Materiały źródłowe

• #1 Glioblastoma Multiforme – AANS

  https://www.aans.org/patients/conditions-treatments/glioblastoma-multiforme/

  Glioblastoma (GBM), also referred to as a grade IV astrocytoma, is a fast-growing and aggressive brain tumor. It invades the nearby brain tissue, but generally does not spread to distant organs. […] GBM is a devastating brain cancer that can result in death in six months or less, if untreated; hence, it is imperative to seek expert neuro-oncological and neurosurgical care immediately, as this can impact overall survival. […] GBMs present unique treatment challenges due to: […] Migration of malignant cells into adjacent brain tissue. […] Glioblastoma is the most common malignant brain and other CNS tumors accounting for 47.7% of all cases. […] Factors associated with glioblastoma risk are prior therapeutic radiation, decreased susceptibility to allergy and impaired immune response.

• #2 Glioblastoma Multiforme Study – NCI

  https://www.cancer.gov/ccg/research/genome-sequencing/tcga/studied-cancers/glioblastoma-multiforme-study

  Glioblastoma Multiforme (GBM) is a fast-growing type of malignant brain tumor that is the most common brain tumor in adults. […] Patients with GBM have a poor prognosis and usually survive less than 15 months following diagnosis. […] Selective pressure to lose mismatch repair function may cause some tumors to become resistant to therapy after treatment with a standard chemotherapy called temozolomide. This finding could be used to develop new strategies that will not activate this drug resistance mechanism. […] Alterations of the EGFR gene as well as a region on a chromosome containing MDM2 and CDK4 genes may be important to the development of GBM. […] GBM mutations are enriched for chromatin modification genes.

• #3 Brain tumor – Wikipedia

  https://en.wikipedia.org/wiki/Brain_tumor

  Secondary, or metastatic, brain tumors are about four times as common as primary brain tumors, with about half of metastases coming from lung cancer. […] The prognosis of brain cancer depends on the type of cancer diagnosed. Medulloblastoma has a good prognosis with chemotherapy, radiotherapy, and surgical resection while glioblastoma has a median survival of only 15 months even with aggressive chemoradiotherapy and surgery.

• #4 Glioblastoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/283252-overview

  Glioblastomas are among the most malignant of human neoplasms and have one of the worst survival rates of any brain tumor. […] Recurrence, or regrowth of tumor after a period of complete remission or stable disease, is nearly universal in glioblastoma and typically occurs within 7 months of initial treatment. […] While the past few decades have seen marginal improvements in overall survival, new approaches to the management of glioblastoma are clearly needed.

• #5 Glioblastoma Multiforme – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558954/

  Glioblastoma multiforme (GBM) is the most malignant and pervasive subtype of glioma and is the most common primary brain tumor in adults. […] The only well-established causative factor is exposure to high doses of ionizing radiation. […] GBM shows features of immune escape and high tumor heterogeneity. Moreover, the relative immune privileged milieu owing to the lack of antigen-presenting cells (APCs) and lymphatics within the CNS further contributes to the poor prognosis among cohorts with GBM. […] Malignant cells have abnormal proliferation, growth, and angiogenesis due to mutations. […] GBM is found to have many genetic and epigenetic mutations. The mutations are essential to identify and classify to understand the tumor behavior and treatment resistance throughout the clinical course.

• #6 Brain Tumors – AANS

  https://www.aans.org/patients/conditions-treatments/brain-tumors/

  Gliomas are the most prevalent type of adult brain tumor, accounting for 78 percent of malignant brain tumors. They arise from the supporting cells of the brain, called the glia. These cells are subdivided into astrocytes, ependymal cells and oligodendroglial cells (or oligos). […] Glioblastoma multiforme (GBM) is the most invasive type of glial tumor. These tumors tend to grow rapidly, spread to other tissue and have a poor prognosis. They may be composed of several different kinds of cells, such as astrocytes and oligodendrocytes. GBM is more common in people ages 50 to 70 and are more prevalent in men than women. […] Brain tumors are thought to arise when certain genes on the chromosomes of a cell are damaged and no longer function properly. These genes normally regulate the rate at which the cell divides (if it divides at all) and repair genes that fix defects of other genes, as well as genes that should cause the cell to self-destruct if the damage is beyond repair.

• #7 Primary Brain Tumors in Adults: Diagnosis and Treatment | AAFP

  https://www.aafp.org/pubs/afp/issues/2016/0201/p211.html

  There are many hypotheses about the pathogenesis of primary brain tumors; genetics clearly play a role in their development. Exposure to high-dose ionizing radiation is the only proven environmental risk factor for primary brain tumors. […] The World Health Organization classifies primary brain tumors based on histopathologic criteria and immunohistochemical data; a malignancy grade is also assigned to tumors, defined by a combination of morphological features, growth patterns, and molecular profile. […] Brain cancers do not conform to a standard staging system. Although they may spread to other parts of the brain or spinal cord, they rarely spread beyond that.

• #8 Glioblastoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/283252-overview

  The p53 pathway is an essential component of DNA repair, cell cycle arrest, and apoptosis. Alterations in this pathway are extremely common, occurring in nearly 90% of glioblastomas. […] The PI3K pathway, an important regulator of cellular proliferation, is activated by RAS and/or receptor tyrosine kinases and inhibited by the tumor suppressor gene PTEN, which is located on the long arm of chromosome 10. […] The only established non-genetic risk factor for glioblastoma is ionizing radiation to the head or neck. […] Although concerns have been raised regarding cell phone use as a potential risk factor for development of gliomas, study results have been inconsistent, and this possibility remains controversial. […] Glioblastoma is the most frequent malignant brain tumor in adults, accounting for approximately 12-15% of all primary intracranial neoplasms and 45-55% of all gliomas.

• #9 Glioblastoma – Wikipedia

  https://en.wikipedia.org/wiki/Glioblastoma

  Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival. […] The cause of most cases of glioblastoma is not known. Uncommon risk factors include genetic disorders, such as neurofibromatosis and LiFraumeni syndrome, and previous radiation therapy. […] Glioblastomas represent 15% of all brain tumors. They are thought to arise from astrocytes. […] The cellular origin of glioblastoma is unknown. Because of the similarities in immunostaining of glial cells and glioblastoma, gliomas such as glioblastoma have long been assumed to originate from glial-type stem cells found in the subventricular zone. More recent studies suggest that astrocytes, oligodendrocyte progenitor cells, and neural stem cells could all serve as the cell of origin.

• #10 Glioblastoma – Wikipedia

  https://en.wikipedia.org/wiki/Glioblastoma

  GBMs usually form in the cerebral white matter, grow quickly, and can become very large before producing symptoms. […] Once cancerous, these cells are predisposed to spread along existing paths in the brain, typically along white-matter tracts, blood vessels and the perivascular space. […] Glioblastoma has been associated with the viruses SV40, HHV-6, and cytomegalovirus (CMV). Infection with an oncogenic CMV may even be necessary for the development of glioblastoma. […] Glioblastoma cells with properties similar to progenitor cells (glioblastoma cancer stem cells) have been found in glioblastomas. Their presence, coupled with the glioblastoma’s diffuse nature results in difficulty in removing them completely by surgery, and is therefore believed to be the possible cause behind resistance to conventional treatments, and the high recurrence rate.

• #11 Why Do Brain Tumors Often Return After Treatment? MSK Researchers Say Stem Cells May Be Key | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/news/why-do-brain-tumors-often-return-after-treatment-msk-researchers-say-stem-cells-may-be-key

  Glioblastoma brain tumors are one of the most deadly forms of cancer, with a five-year survival rate of less than 10% for patients 45 and older. Even when the tumors look as if they have been fully removed, they almost always come back. […] The standard therapy for glioblastoma targets actively dividing cells, says BTC Director Luis Parada, the papers senior author, who came to MSK in 2015 to develop a comprehensive program for fighting brain tumors. But here, we demonstrate the existence of a small percentage of dormant, stem-like cells that evade these therapies and reinitiate tumor development. […] Traditional chemotherapy and radiation therapy go after cells that are quickly growing and dividing a characteristic of most cancer cells. But in glioblastoma tumors, some cells are quiescent. That means they are essentially in a dormant, resting state hiding out from treatments aimed at cell division.

• #12 Why Do Brain Tumors Often Return After Treatment? MSK Researchers Say Stem Cells May Be Key | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/news/why-do-brain-tumors-often-return-after-treatment-msk-researchers-say-stem-cells-may-be-key

  We found that quiescent cells very gradually give rise to dividing cells, which allow tumors to grow again, explains Dr. Parada, who is a member of the Cancer Biology and Genetics Program in the Sloan Kettering Institute. […] This research shows why therapies that focus only on cell division are insufficient for treating glioblastoma and reinforce the need for developing new strategies that target quiescent cells, Dr. Parada says. The discovery of activated cancer stem cells in mouse models provides us with unprecedented opportunity to investigate their unique features and self-renewal mechanisms, which will help in our ongoing efforts to find a cure for glioblastoma.

• #13 Issues Related to the Study of Malignant Brain Tumors

  https://www.barrowneuro.org/for-physicians-researchers/education/grand-rounds-publications-media/barrow-quarterly/volume-14-no-2-1998/issues-related-study-malignant-brain-tumors/

  Cancer appears to result from the accumulation of multiple genetic alterations. Malignant brain tumors likewise develop sequential aberrations that contribute to malignant progression. Brain cancer is unregulated cell proliferation with the additional property of invasiveness. Consequently, a broader spectrum of characterizations with the biology of brain tumors must be considered to determine which of the dynamic mechanisms creates the malignant phenotype. […] The genetic aberrations associated with this process are best known for leukemias and lymphomas. Similar information about solid tumors has lagged behind. […] Despite these difficulties, our understanding is being advanced by new technologies that require less tissue for analysis and that permit the use of archival samples, which often supply extensive history about patients.

• #14 Issues Related to the Study of Malignant Brain Tumors

  https://www.barrowneuro.org/for-physicians-researchers/education/grand-rounds-publications-media/barrow-quarterly/volume-14-no-2-1998/issues-related-study-malignant-brain-tumors/

  In brain tumors, genomic instability appears to be more important to progression rather than to the initiation of a tumor. […] The concept that tumors progress to a more malignant state by the acquisition of mutations is not new. […] The mechanisms underlying this genetic variability are areas of intense research. […] In gliomas, telomerase is seldom amplified although about 60% of gliomas show alterations in telomeric length. […] A breakdown in any one of these mechanisms has been attributed to genomic instability. […] Two general categories of genes are directly involved in transformation and progression of the malignant process by one or more of the mechanisms described above. Oncogenes are genes capable of transforming a eukaryotic cell into a cell that grows in a manner analogous to tumor cells, while tumor suppressor genes are genes capable of suppressing tumor formation.

• #15 Glioblastoma – Wikipedia

  https://en.wikipedia.org/wiki/Glioblastoma

  Another important alteration is methylation of MGMT, a „suicide” DNA repair enzyme. Methylation impairs DNA transcription and expression of the MGMT gene. […] Many other genetic alterations have been described in glioblastoma, and the majority of them are clustered in two pathways, the RB and the PI3K/AKT. […] The first pathway involves the amplification and mutational activation of receptor tyrosine kinase (RTK) genes, leading to the dysregulation of growth factor signaling. […] The second method involves activating the intracellular signaling system known as phosphatidylinositol-3-OH kinase (PI3K)/AKT/mTOR, which is crucial for controlling cell survival. […] The third pathway is defined by p53 and retinoblastoma (Rb) tumor suppressor pathway inactivation.

• #16 Autophagy in cancers including brain tumors: role of MicroRNAs | Cell Communication and Signaling | Full Text

  https://biosignaling.biomedcentral.com/articles/10.1186/s12964-020-00587-w

  The most frequent genetic alterations/mutations found in gliomas are: hemizygous/homozygous deletion of NF-1 and PTEN; EGFR vIII mutant expression; and EGFR amplification. […] The abnormal signaling resulting from such mutations interacts with PI3K-Akt-mTOR pathways that promotes chemo-resistance and survival in gliomas. […] The Cancer Genome Atlas consortium categorized glioblastoma (GBM) tumors into four molecular sub-types, including neural, classical, mesenchymal, and proneural. […] The particular role of autophagy in contributing to cell death or cell survival in different therapeutic approaches is yet to be fully explained, and a better understanding of these contrary findings is essential to design potential combination therapies. […] MiR-93 modulated autophagy functions in GSCs by synchronized suppression of several autophagy modulators, such as SQSTM1/p62, ATG4B, ATG5 and BECN1/beclin 1.

• #17 Issues Related to the Study of Malignant Brain Tumors

  https://www.barrowneuro.org/for-physicians-researchers/education/grand-rounds-publications-media/barrow-quarterly/volume-14-no-2-1998/issues-related-study-malignant-brain-tumors/

  Proto-oncogenes become oncogenes when they are activated by mutation or by increasing the copy number (gene amplification). […] Approximately 100 oncogenes have been identified, several of which are aberrantly expressed in brain tumors. […] Several mechanisms underlie the failure of a tumor suppressor gene to function normally. […] The first evidence that loss of a tumor suppressor gene causes tumor formation came from retinoblastomas, neoplasms that can occur in either familial or sporadic forms. […] The multistep process of transforming a normal cell, either in vitro or in vivo, requires a series of changes in both oncogenes and tumor suppressor genes. […] When the genes controlling apoptosis are deregulated, cells develop inappropriate survival and tumorigenic properties. […] More than a third to half of all grade II to IV malignant gliomas have a mutation in TP53 or have lost one or both alleles. […] An early change in the evolution of gliomas, this aberration is typically associated with a less favorable prognosis. […] Understanding how and where gene(s) function can provide the means to eradicate tumor cells in the future.

• #18 Glioblastoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/283252-overview

  The p53 pathway is an essential component of DNA repair, cell cycle arrest, and apoptosis. Alterations in this pathway are extremely common, occurring in nearly 90% of glioblastomas. […] The PI3K pathway, an important regulator of cellular proliferation, is activated by RAS and/or receptor tyrosine kinases and inhibited by the tumor suppressor gene PTEN, which is located on the long arm of chromosome 10. […] The only established non-genetic risk factor for glioblastoma is ionizing radiation to the head or neck. […] Although concerns have been raised regarding cell phone use as a potential risk factor for development of gliomas, study results have been inconsistent, and this possibility remains controversial. […] Glioblastoma is the most frequent malignant brain tumor in adults, accounting for approximately 12-15% of all primary intracranial neoplasms and 45-55% of all gliomas.

• #19 Glioblastoma: Overview of Disease and Treatment | Oncology Nursing Society

  https://www.ons.org/publications-research/cjon/20/5/supplement-october-2016-glioblastoma-treatment/glioblastoma

  Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. […] Significant advances in the understanding of the molecular pathology of GBM and associated cell signaling pathways have opened opportunities for new therapies for recurrent and newly diagnosed disease. […] The majority of primary and secondary GBMs have alterations in these pathways, giving rise to uncontrolled cell proliferation and enhanced cell survival, while also allowing the tumor cell to escape from cell-cycle checkpoints, senescence, and apoptosis pathways. […] Genetic alterations typical for primary GBM are epidermal growth factor receptor (EGFR) overexpression, phosphate and tensin homologue (PTEN) mutations, and loss of chromosome 10q. […] In secondary GBM, isocitrate dehydrogenase 1 (IDH1) mutations, p53 mutations, and chromosome 19q loss are frequently seen.

• #20 Brain Tumor Glossary

  https://braintumor.org/brain-tumors/diagnosis-treatment/diagnosis/brain-tumor-glossary/

  Malignant Brain Tumors contain cancer cells and often do not have clear borders. They are considered to be life-threatening because they grow rapidly and invade surrounding brain tissue. Although malignant brain tumors very rarely spread to other areas of the body, they can spread throughout the brain or to the spine. These tumors can be treated with surgery, chemotherapy and radiation, but they may recur after treatment. […] IDH has three forms, IDH1, IDH2, and IDH3. Mutated forms of IDH1 and IDH2 are often found in gliomas, typically low-grade gliomas and secondary glioblastomas (though IDH1 mutations are occasionally found in primary GBM patients, as well). These mutations, which occur early in the tumor-forming process, change the function of the enzymes, causing them to produce a metabolite called 2-hydroxyglutarate (2HG), instead of a molecule called NADPH. The presence of an IDH mutation in patients tumors is a biomarker for improved prognosis. This means that glioma patients that have an IDH mutation tend to live longer than patients without an IDH mutation (IDH-wide-type). […] Tumorigenesis is the process of transformation of normal cells into tumor cells.

• #21 Signaling pathways in brain tumors and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01260-z

  Grading using Arabic numerals is recommended, as highlighted by WHO CNS5. […] GBM accounts for 57% of all gliomas while 48% of primary CNS malignancies in HGG, have a median survival time of fewer than 2 years. […] O6 methylguanine DNA methyltransferase (MGMT) is a repair protein that is encoded by the MGMT gene, which can reverse DNA alkylation by depleting itself. […] In patients with MGMT promoter methylation found in 30-50% of isocitrate dehydrogenase (IDH)-wt GBM, gene promoter methylation would repress the expression of this gene. […] Therefore, with MGMT promoter methylation, glioma patients benefit more from treatment with TMZ. […] However, a discordance of MGMT promoter methylation with protein expression was detected in various patient. […] This may be related to the regulation of MGMT protein by Wnt signaling in addition to the regulation of MGMT promoter methylation.

• #22 Glioblastoma: Overview of Disease and Treatment | Oncology Nursing Society

  https://www.ons.org/publications-research/cjon/20/5/supplement-october-2016-glioblastoma-treatment/glioblastoma

  An analysis by Johnson and ONeill (2012) demonstrated a statistically significant improvement in OS since the onset of aggressive multimodality treatment. […] The analysis of this trial also led to the identification of another strong predictor of patient-related outcomes: the methylation of the MGMT gene, located on chromosome 10q26. […] Patients who have methylated (not activated) MGMT exhibit compromised DNA repair. […] Therefore, the expression of methylated MGMT is beneficial for patients undergoing TMZ chemotherapy and RT. […] Despite maximal initial resection and multimodality therapy, about 70% of GBM patients will experience disease progression within one year of diagnosis. […] Re-resection is an option for some patients, and surgical debulking can alleviate mass effect and symptoms, such as seizures, speech, and motor deficits, frequently seen at recurrence.

• #23 An Overview of Brain Tumor | IntechOpen

  https://www.intechopen.com/chapters/79979

  Most signaling pathways and physiological responses, including migration, proliferation, survival, and tumor development, are activated by the epidermal growth factor receptor (EGFR). […] Isocitrate dehydrogenase (IDH) is a protein enzyme that encodes genes on chromosome 2, the main function of IDH in the Krebs cycle is to catalyze oxidative decarboxylation. […] Cell-free DNA (cfDNA) as a double-stranded, DNA fragments released for the breakdown of cancer tissue by bloodstream that is approximately 150 to 200 base pairs in length, corresponding to nucleosome-associated DNA, can be released by cells under physiological and pathological conditions as well. […] Several tumor-derived circulating nucleic acids (e.g., ctDNA, cmtDNA, mRNA, non-coding RNAs including miRNAs, long non-coding RNAs) that can be detected from blood or other types of body fluids like urine, cerebrospinal fluid (CSF), saliva, pleural fluid, and ascites.

• #24 Neuro-ophthalmic Manifestations of Glioblastoma Multiforme – EyeWiki

  https://eyewiki.org/Neuro-ophthalmic_Manifestations_of_Glioblastoma_Multiforme

  Glioblastoma multiforme (GBM) is a Grade IV astrocytoma and represents the most common primary malignant brain tumor in adults. […] In general, gliomas undergo malignant transformation through the sequential accumulation of genetic mutations and abnormal regulation of growth factor signaling pathways. […] GBM has two clinical forms primary and secondary GBM. Primary GBM usually arises de novo and often has amplified, mutated epidermal-growth factor receptor (EGFR), whereas secondary GBM arises from prior low-grade astrocytoma and often has increased platelet-derived growth factor A (PDGF-A) receptor signaling. […] Even though primary and secondary GBM have different mutations in their pathogenesis, they both result in aberrations in the same signaling pathways, ultimately resulting in increased cell proliferation, inhibition of apoptosis, invasion, and angiogenesis.

• #25 Glioblastoma: Overview of Disease and Treatment | Oncology Nursing Society

  https://www.ons.org/publications-research/cjon/20/5/supplement-october-2016-glioblastoma-treatment/glioblastoma

  Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. […] Significant advances in the understanding of the molecular pathology of GBM and associated cell signaling pathways have opened opportunities for new therapies for recurrent and newly diagnosed disease. […] The majority of primary and secondary GBMs have alterations in these pathways, giving rise to uncontrolled cell proliferation and enhanced cell survival, while also allowing the tumor cell to escape from cell-cycle checkpoints, senescence, and apoptosis pathways. […] Genetic alterations typical for primary GBM are epidermal growth factor receptor (EGFR) overexpression, phosphate and tensin homologue (PTEN) mutations, and loss of chromosome 10q. […] In secondary GBM, isocitrate dehydrogenase 1 (IDH1) mutations, p53 mutations, and chromosome 19q loss are frequently seen.

• #26 Neuro-ophthalmic Manifestations of Glioblastoma Multiforme – EyeWiki

  https://eyewiki.org/Neuro-ophthalmic_Manifestations_of_Glioblastoma_Multiforme

  Glioblastoma multiforme (GBM) is a Grade IV astrocytoma and represents the most common primary malignant brain tumor in adults. […] In general, gliomas undergo malignant transformation through the sequential accumulation of genetic mutations and abnormal regulation of growth factor signaling pathways. […] GBM has two clinical forms primary and secondary GBM. Primary GBM usually arises de novo and often has amplified, mutated epidermal-growth factor receptor (EGFR), whereas secondary GBM arises from prior low-grade astrocytoma and often has increased platelet-derived growth factor A (PDGF-A) receptor signaling. […] Even though primary and secondary GBM have different mutations in their pathogenesis, they both result in aberrations in the same signaling pathways, ultimately resulting in increased cell proliferation, inhibition of apoptosis, invasion, and angiogenesis.

• #27 Molecular Determinants of Malignant Brain Cancers: From Intracellular Alterations to Invasion Mediated by Extracellular Vesicles

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5751372/

  Malignant glioma cells invade the surrounding brain parenchyma, by migrating along the blood vessels, thus promoting cancer growth. […] The biological bases of these activities are grounded in profound alterations of the metabolism and the structural organization of the cells, which consequently acquire the ability to modify the surrounding microenvironment, by altering the extracellular matrix and affecting the properties of the other cells present in the brain, such as normal glial-, endothelial- and immune-cells. […] Most of the effects on the surrounding environment are probably exerted through the release of a variety of extracellular vesicles (EVs), which contain many different classes of molecules, from genetic material to defined species of lipids and enzymes. […] In order to invade the brain parenchyma, glioma cells must modify their own interactions with the ECM and the ECM itself, which in the brain has a peculiar composition.

• #28 Molecular Determinants of Malignant Brain Cancers: From Intracellular Alterations to Invasion Mediated by Extracellular Vesicles

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5751372/

  Moreover, the rapid proliferation of the malignant cells per se has a metabolic effect on the microenvironment, which is rapidly deprived of glucose and oxygen, becoming acidic and hypoxic. […] These modifications are part of the so called epithelial-mesenchymal transition (EMT), which, although its role in glioma is still controversial, seems to be determinant for the degree of malignancy. […] At the base of invasion and progression of glial tumors there is a continuous interaction between neoplastic cells and ECM. […] A variety of ECM components have been found to be either up- or down-regulated in brain tumors and have been therefore considered as possible key molecules in the mechanism of invasion of malignant glial tumors. […] Glioma cell invasion into the surrounding parenchyma requires, besides modifications of the cell shape and production of invadopodia, also adjustment of cell volume.

• #29 Cancers | Special Issue : Resistance Mechanisms in Malignant Brain Tumors

  https://www.mdpi.com/journal/cancers/special_issues/Resistance_Mechanism_Malignant_Brain_Tumor

  Tumor microenvironment effects mediated by the complex crosstalk between tumor and non-malignant cells including astrocytes, neurons, vasculature (endothelial cells and pericytes), as well as distinct immune compartment of the brain comprising microglia, resident and blood-recruited macrophages and lymphocytes. […] Microanatomical and biomechanical features of the tumor itself, such as the inefficient drug delivery, hypoxia and acidosis, tumor infiltration and invasion, vessel co-option and angiogenesis. […] This Special Issue will focus on the tumor features and mechanisms that convey resistance to therapy in malignant brain tumors.

• #30 Brain Tumors – AANS

  https://www.aans.org/patients/conditions-treatments/brain-tumors/

  Once a cell is dividing rapidly and internal mechanisms to check its growth are damaged, the cell can eventually grow into a tumor. Another line of defense may be the body’s immune system, which optimally would detect the abnormal cell and kill it. Tumors may produce substances that block the immune system from recognizing the abnormal tumor cells and eventually overpower all internal and external deterrents to its growth. […] A rapidly growing tumor may need more oxygen and nutrients than can be provided by the local blood supply intended for normal tissue. Tumors can produce substances called angiogenesis factors that promote the growth of blood vessels. The new vessels that grow increase the supply of nutrients to the tumor, and, eventually, the tumor becomes dependent on these new vessels. Research is being done in this area, but more extensive research is necessary to translate this knowledge into potential therapies.

• #31 Signaling pathways in brain tumors and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01260-z

  The production of R-2HG makes IDH mutant cells sensitive to alkylating agents. […] The clinically significant bifunctional alkylating agents procarbazine and CCNU/lomustine induces highly genotoxic DNA interstrand crosslinks, and are a part of the PCV chemotherapeutic regimen successfully utilized in combination with radiotherapy for the treatment of brain tumors with IDH mutation status. […] The vascular endothelial growth factor receptor (VEGFR) signaling pathway has been considered a key factor in GBM tumor survival. […] Bevacizumab inhibits angiogenesis by acting as a humanized monoclonal antibody against the VEGF-A ligand. […] The transforming growth factor beta (TGF-) protein family has complicated functions in diverse regulatory pathways, where TGF-2 is a T cell inhibitor in the GBM tumor microenvironment that is found in approximately 90% of GBM tumor cells. […] The above crucial signaling pathways involved in glioma were demonstrated in Fig. 2.

• #32 Brain Neoplasms: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/779664-overview

  Tumors of the brain produce neurologic manifestations through a number of mechanisms. Small, critically located tumors may damage specific neural pathways traversing the brain. Tumors can invade, infiltrate, or supplant normal parenchymal tissue, disrupting normal function. Because the brain dwells in the limited volume of the cranial vault, growth of intracranial tumors with accompanying edema may cause increased intracranial pressure. Tumors adjacent to the third and fourth ventricles may impede the flow of cerebrospinal fluid, leading to obstructive hydrocephalus. In addition, tumors generate new blood vessels (ie, angiogenesis), disrupting the normal blood-brain barrier and promoting edema. […] The cumulative effects of tumor invasion, edema, and hydrocephalus may elevate the intracranial pressure (ICP) and impair cerebral perfusion. Intracranial compartmental rise in ICP may provoke shifting or herniation of tissue under the falx cerebri, through the tentorium cerebelli, or through the foramen magnum.

• #33 ADAR1 inhibition: Hijacking an innate immune mechanism present in all malignant cells | The Brain Tumour Charity Research Project

  https://www.thebraintumourcharity.org/brain-tumour-diagnosis-treatment/types-of-brain-tumour-adult/glioblastoma/glioblastoma-research/hijacking-innate-immune-mechanism-in-malignant-cells/

  Glioblastomas are incurable brain tumours. […] New therapeutic strategies have instead advanced towards exploiting the immune system to fight glioblastoma tumours. […] The hypothesis is that getting rid of ADAR1 in cancer cells would confound cancer cells defence mechanisms. […] The lost ability to recognise molecules produced during normal physiological processes would lead to an increase vulnerability of cancer cells. […] The tumour microenvironment (TME) around glioblastoma cells is often highly immunosuppressive. […] By reprogramming the immune microenvironment to fight cancer cells, TME-targeted immunotherapies could overcome the immunosuppressive nature of the microenvironment and enhance the effectiveness of ADAR1 inhibition. […] Dr lvarez-Prados project is critical in developing new therapeutic approaches that simultaneously target cancer cells and their supporting microenvironment. […] This project could lead to more effective treatment for patients, by simultaneously attacking cancer cells from the inside and outside, and would be less toxic, as it exploits a vulnerability present within glioblastoma cells.

• #34 Signaling pathways in brain tumors and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01260-z

  The production of R-2HG makes IDH mutant cells sensitive to alkylating agents. […] The clinically significant bifunctional alkylating agents procarbazine and CCNU/lomustine induces highly genotoxic DNA interstrand crosslinks, and are a part of the PCV chemotherapeutic regimen successfully utilized in combination with radiotherapy for the treatment of brain tumors with IDH mutation status. […] The vascular endothelial growth factor receptor (VEGFR) signaling pathway has been considered a key factor in GBM tumor survival. […] Bevacizumab inhibits angiogenesis by acting as a humanized monoclonal antibody against the VEGF-A ligand. […] The transforming growth factor beta (TGF-) protein family has complicated functions in diverse regulatory pathways, where TGF-2 is a T cell inhibitor in the GBM tumor microenvironment that is found in approximately 90% of GBM tumor cells. […] The above crucial signaling pathways involved in glioma were demonstrated in Fig. 2.

• #35 Glioblastoma Multiforme – AANS

  https://www.aans.org/patients/conditions-treatments/glioblastoma-multiforme/

  Next generation sequencing aids molecular analysis and in profiling brain tumors to improve diagnostic accuracy, therapeutic target identification and predict prognosis. […] The mainstay of treatment for GBMs is surgery, followed by radiation and chemotherapy. […] However, GBMs are surrounded by a zone of migrating, infiltrating tumor cells that invade surrounding tissues, making it impossible to ever remove the tumor entirely. […] The use of radiation therapy provides most patients with improved outcomes and longer survival rates compared to surgery alone or the best supportive care. […] Chemotherapy with the drug temozolomide is the current standard of treatment for GBM.

• #36 Glioblastoma – Wikipedia

  https://en.wikipedia.org/wiki/Glioblastoma

  GBMs usually form in the cerebral white matter, grow quickly, and can become very large before producing symptoms. […] Once cancerous, these cells are predisposed to spread along existing paths in the brain, typically along white-matter tracts, blood vessels and the perivascular space. […] Glioblastoma has been associated with the viruses SV40, HHV-6, and cytomegalovirus (CMV). Infection with an oncogenic CMV may even be necessary for the development of glioblastoma. […] Glioblastoma cells with properties similar to progenitor cells (glioblastoma cancer stem cells) have been found in glioblastomas. Their presence, coupled with the glioblastoma’s diffuse nature results in difficulty in removing them completely by surgery, and is therefore believed to be the possible cause behind resistance to conventional treatments, and the high recurrence rate.

• #37 Molecular Determinants of Malignant Brain Cancers: From Intracellular Alterations to Invasion Mediated by Extracellular Vesicles

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5751372/

  Moreover, the rapid proliferation of the malignant cells per se has a metabolic effect on the microenvironment, which is rapidly deprived of glucose and oxygen, becoming acidic and hypoxic. […] These modifications are part of the so called epithelial-mesenchymal transition (EMT), which, although its role in glioma is still controversial, seems to be determinant for the degree of malignancy. […] At the base of invasion and progression of glial tumors there is a continuous interaction between neoplastic cells and ECM. […] A variety of ECM components have been found to be either up- or down-regulated in brain tumors and have been therefore considered as possible key molecules in the mechanism of invasion of malignant glial tumors. […] Glioma cell invasion into the surrounding parenchyma requires, besides modifications of the cell shape and production of invadopodia, also adjustment of cell volume.

• #38 Molecular Determinants of Malignant Brain Cancers: From Intracellular Alterations to Invasion Mediated by Extracellular Vesicles

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5751372/

  Malignant glioma cells invade the surrounding brain parenchyma, by migrating along the blood vessels, thus promoting cancer growth. […] The biological bases of these activities are grounded in profound alterations of the metabolism and the structural organization of the cells, which consequently acquire the ability to modify the surrounding microenvironment, by altering the extracellular matrix and affecting the properties of the other cells present in the brain, such as normal glial-, endothelial- and immune-cells. […] Most of the effects on the surrounding environment are probably exerted through the release of a variety of extracellular vesicles (EVs), which contain many different classes of molecules, from genetic material to defined species of lipids and enzymes. […] In order to invade the brain parenchyma, glioma cells must modify their own interactions with the ECM and the ECM itself, which in the brain has a peculiar composition.

• #39 Molecular Determinants of Malignant Brain Cancers: From Intracellular Alterations to Invasion Mediated by Extracellular Vesicles

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5751372/

  Glioma cells can also cause ECM remodeling in an indirect manner: glioma cell-derived vesicles can indeed induce in vitro adjacent cells, in particular cancer-associated fibroblasts (CAF), to secrete components of the ECM. […] Tumor cells are able to modify ECM by producing EVs that contain extracellular proteins, such as the extracellular matrix protein 1 (ECM-1) and Collagen IV, as well as ECM remodeling enzymes. […] Cancer cells can also cause ECM remodeling in an indirect manner: glioma cell-derived vesicles can indeed induce in vitro adjacent cells, in particular cancer-associated fibroblasts (CAF), to secrete components of the ECM. […] The ability of cancer cells to invade the healthy brain tissue is a pathologic property of gliomas that contributes to the failure of the therapies currently adopted for the patients and essentially based on surgery, followed by radiotherapy and/or chemotherapy.

• #40 Molecular Determinants of Malignant Brain Cancers: From Intracellular Alterations to Invasion Mediated by Extracellular Vesicles

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5751372/

  Moreover, the rapid proliferation of the malignant cells per se has a metabolic effect on the microenvironment, which is rapidly deprived of glucose and oxygen, becoming acidic and hypoxic. […] These modifications are part of the so called epithelial-mesenchymal transition (EMT), which, although its role in glioma is still controversial, seems to be determinant for the degree of malignancy. […] At the base of invasion and progression of glial tumors there is a continuous interaction between neoplastic cells and ECM. […] A variety of ECM components have been found to be either up- or down-regulated in brain tumors and have been therefore considered as possible key molecules in the mechanism of invasion of malignant glial tumors. […] Glioma cell invasion into the surrounding parenchyma requires, besides modifications of the cell shape and production of invadopodia, also adjustment of cell volume.

• #41 Long Non-Coding RNAs in Malignant Human Brain Tumors: Driving Forces Behind Progression and Therapy

  https://www.mdpi.com/1422-0067/26/2/694

  The expression of LINC00461 is markedly elevated in stem cell-like GB cells, correlating with cell proliferation and drug resistance. […] The epithelial-to-mesenchymal transition (EMT) mechanism acts as a key driver of tumor cell metastasis, with dysregulated EMT processes closely associated with tumor migration and invasion. […] In glioblastoma, the N6-methyladenosine (m6A)-modified LINREP interacts with the PTBP1/HuR complex and protects PTBP1 from ubiquitin-mediated degradation, thereby promoting tumor progression and potentially serving as a novel therapeutic target. […] The research discovered a new cancer-related lncRNA called EPAT that prevents USP16 from deubiquitinating H2A and suppresses the expression of certain genes. […] In glioblastoma, exosomes containing lncRNAs induce microglia to produce complement C5, promoting chemotherapy resistance.

• #42 Molecular Determinants of Malignant Brain Cancers: From Intracellular Alterations to Invasion Mediated by Extracellular Vesicles

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5751372/

  Malignant glioma cells invade the surrounding brain parenchyma, by migrating along the blood vessels, thus promoting cancer growth. […] The biological bases of these activities are grounded in profound alterations of the metabolism and the structural organization of the cells, which consequently acquire the ability to modify the surrounding microenvironment, by altering the extracellular matrix and affecting the properties of the other cells present in the brain, such as normal glial-, endothelial- and immune-cells. […] Most of the effects on the surrounding environment are probably exerted through the release of a variety of extracellular vesicles (EVs), which contain many different classes of molecules, from genetic material to defined species of lipids and enzymes. […] In order to invade the brain parenchyma, glioma cells must modify their own interactions with the ECM and the ECM itself, which in the brain has a peculiar composition.

• #43 Molecular Determinants of Malignant Brain Cancers: From Intracellular Alterations to Invasion Mediated by Extracellular Vesicles

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5751372/

  Glioma cells can also cause ECM remodeling in an indirect manner: glioma cell-derived vesicles can indeed induce in vitro adjacent cells, in particular cancer-associated fibroblasts (CAF), to secrete components of the ECM. […] Tumor cells are able to modify ECM by producing EVs that contain extracellular proteins, such as the extracellular matrix protein 1 (ECM-1) and Collagen IV, as well as ECM remodeling enzymes. […] Cancer cells can also cause ECM remodeling in an indirect manner: glioma cell-derived vesicles can indeed induce in vitro adjacent cells, in particular cancer-associated fibroblasts (CAF), to secrete components of the ECM. […] The ability of cancer cells to invade the healthy brain tissue is a pathologic property of gliomas that contributes to the failure of the therapies currently adopted for the patients and essentially based on surgery, followed by radiotherapy and/or chemotherapy.

• #44 Cancers | Special Issue : Resistance Mechanisms in Malignant Brain Tumors

  https://www.mdpi.com/journal/cancers/special_issues/Resistance_Mechanism_Malignant_Brain_Tumor

  Resistance Mechanisms in Malignant Brain Tumors […] Brain tumors comprise a broad range of primary and metastatic tumors, with different aggressiveness and clinical outcomes. Glioblastoma (GBM), and secondary metastatic tumors from distant organs, such as melanoma, lymphoma, lung and breast cancers, are among the most deadly and incurable types of human cancer. […] The standard treatments are currently not effective, because malignant brain tumors are highly resistant to therapies, such as radiation, chemo- and immunotherapy. The mechanisms of resistance can be intrinsic or acquired and include: […] Cell-autonomous mechanisms, involving undruggable genomic drivers and pathway reactivation, genomic instability, DNA damage response, intra- and inter-tumor heterogeneity, stem cell features, epigenetics and phenotypic plasticity.

• #45 Cancers | Special Issue : Resistance Mechanisms in Malignant Brain Tumors

  https://www.mdpi.com/journal/cancers/special_issues/Resistance_Mechanism_Malignant_Brain_Tumor

  Resistance Mechanisms in Malignant Brain Tumors […] Brain tumors comprise a broad range of primary and metastatic tumors, with different aggressiveness and clinical outcomes. Glioblastoma (GBM), and secondary metastatic tumors from distant organs, such as melanoma, lymphoma, lung and breast cancers, are among the most deadly and incurable types of human cancer. […] The standard treatments are currently not effective, because malignant brain tumors are highly resistant to therapies, such as radiation, chemo- and immunotherapy. The mechanisms of resistance can be intrinsic or acquired and include: […] Cell-autonomous mechanisms, involving undruggable genomic drivers and pathway reactivation, genomic instability, DNA damage response, intra- and inter-tumor heterogeneity, stem cell features, epigenetics and phenotypic plasticity.

• #46 Frontiers | Iron Transporters and Ferroptosis in Malignant Brain Tumors

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.861834/full

  Malignant brain tumors are commonly intratumoral heterogenic, which likely explains their poor clinical prognosis of malignant brain tumors poor and easy to relapse. Despite current multimodality treatment efforts, combining in surgical resection when feasible, with radiotherapy, chemotherapy and symptomatic treatment, the median survival remains short. […] Ferroptosis occurs when iron overload induces lipid peroxidation. Recent studies showed that ferroptosis is involved in the death of pathological cells in malignant brain tumors, which may have a therapeutic potential towards malignant brain tumors. […] Starting from the iron transport in the body under physiological conditions, we further summarize the specific mechanism of iron metabolism disorder and ferroptosis in the pathological condition of malignant brain tumors, in particular, the crucial role of transporters.

• #47 Glioblastoma – Wikipedia

  https://en.wikipedia.org/wiki/Glioblastoma

  GBMs usually form in the cerebral white matter, grow quickly, and can become very large before producing symptoms. […] Once cancerous, these cells are predisposed to spread along existing paths in the brain, typically along white-matter tracts, blood vessels and the perivascular space. […] Glioblastoma has been associated with the viruses SV40, HHV-6, and cytomegalovirus (CMV). Infection with an oncogenic CMV may even be necessary for the development of glioblastoma. […] Glioblastoma cells with properties similar to progenitor cells (glioblastoma cancer stem cells) have been found in glioblastomas. Their presence, coupled with the glioblastoma’s diffuse nature results in difficulty in removing them completely by surgery, and is therefore believed to be the possible cause behind resistance to conventional treatments, and the high recurrence rate.

• #48 Cancers | Special Issue : Resistance Mechanisms in Malignant Brain Tumors

  https://www.mdpi.com/journal/cancers/special_issues/Resistance_Mechanism_Malignant_Brain_Tumor

  Tumor microenvironment effects mediated by the complex crosstalk between tumor and non-malignant cells including astrocytes, neurons, vasculature (endothelial cells and pericytes), as well as distinct immune compartment of the brain comprising microglia, resident and blood-recruited macrophages and lymphocytes. […] Microanatomical and biomechanical features of the tumor itself, such as the inefficient drug delivery, hypoxia and acidosis, tumor infiltration and invasion, vessel co-option and angiogenesis. […] This Special Issue will focus on the tumor features and mechanisms that convey resistance to therapy in malignant brain tumors.

• #49 Signaling pathways in brain tumors and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01260-z

  Grading using Arabic numerals is recommended, as highlighted by WHO CNS5. […] GBM accounts for 57% of all gliomas while 48% of primary CNS malignancies in HGG, have a median survival time of fewer than 2 years. […] O6 methylguanine DNA methyltransferase (MGMT) is a repair protein that is encoded by the MGMT gene, which can reverse DNA alkylation by depleting itself. […] In patients with MGMT promoter methylation found in 30-50% of isocitrate dehydrogenase (IDH)-wt GBM, gene promoter methylation would repress the expression of this gene. […] Therefore, with MGMT promoter methylation, glioma patients benefit more from treatment with TMZ. […] However, a discordance of MGMT promoter methylation with protein expression was detected in various patient. […] This may be related to the regulation of MGMT protein by Wnt signaling in addition to the regulation of MGMT promoter methylation.

• #50 Cancers | Special Issue : Resistance Mechanisms in Malignant Brain Tumors

  https://www.mdpi.com/journal/cancers/special_issues/Resistance_Mechanism_Malignant_Brain_Tumor

  Resistance Mechanisms in Malignant Brain Tumors […] Brain tumors comprise a broad range of primary and metastatic tumors, with different aggressiveness and clinical outcomes. Glioblastoma (GBM), and secondary metastatic tumors from distant organs, such as melanoma, lymphoma, lung and breast cancers, are among the most deadly and incurable types of human cancer. […] The standard treatments are currently not effective, because malignant brain tumors are highly resistant to therapies, such as radiation, chemo- and immunotherapy. The mechanisms of resistance can be intrinsic or acquired and include: […] Cell-autonomous mechanisms, involving undruggable genomic drivers and pathway reactivation, genomic instability, DNA damage response, intra- and inter-tumor heterogeneity, stem cell features, epigenetics and phenotypic plasticity.

• #51 Autophagy in cancers including brain tumors: role of MicroRNAs | Cell Communication and Signaling | Full Text

  https://biosignaling.biomedcentral.com/articles/10.1186/s12964-020-00587-w

  Autophagy has a crucial role in many cancers, including brain tumors. […] Several studies have revealed the contribution of autophagy in the pathogenesis of brain tumors. […] It has been shown that various cellular and molecular mechanisms are associated with autophagy-related processes in brain tumors and also in other different cancers. […] A variety of miRNAs are able to modulate autophagy, and its related mechanisms in various cancers including brain tumors. […] The poor response of malignant brain tumors to conventional therapies, many of which work by inducing apoptosis, makes it attractive to target autophagy as an alternative mechanism for triggering glioma cell death. […] Alterations or mutations that are commonly found in brain tumors, include p53, PTEN, AKT, NF1 and EGFR, and some of these are accepted to be implicated in the modulation of autophagy.

• #52 Frontiers | Iron Transporters and Ferroptosis in Malignant Brain Tumors

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.861834/full

  Ferroptosis is a form of iron-dependent regulatory cell death distinguished from necrosis, apoptosis and autophagy, which can be triggered by the small-molecule compound erastin and RSL3. Iron and polyunsaturated fatty acids (PUFAs) act as raw materials for lipid peroxidation to promote the occurrence of ferroptosis. […] Ferroptosis plays a key role in the development of malignant brain tumors. As an important part of ferroptosis, relevant transporters can regulate amino acid metabolism and iron metabolism and are essential for the maintenance of iron homeostasis. Disorders of iron homeostasis in the brain will increase the risk of tumors, which may be one of the factors leading to the increased incidence of brain tumors. […] Inducing ferroptosis of tumor cells is a newly discovered strategy for the treatment of malignant brain tumors, but many problems remain to be solved, including elucidating the mechanism of ferroptosis in different malignant brain tumors, discovering new therapeutic targets for inducing ferroptosis of tumor cells, and increasing the tumor cell targeting of ferroptosis inducers.

• #53 Signaling pathways in brain tumors and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01260-z

  Grading using Arabic numerals is recommended, as highlighted by WHO CNS5. […] GBM accounts for 57% of all gliomas while 48% of primary CNS malignancies in HGG, have a median survival time of fewer than 2 years. […] O6 methylguanine DNA methyltransferase (MGMT) is a repair protein that is encoded by the MGMT gene, which can reverse DNA alkylation by depleting itself. […] In patients with MGMT promoter methylation found in 30-50% of isocitrate dehydrogenase (IDH)-wt GBM, gene promoter methylation would repress the expression of this gene. […] Therefore, with MGMT promoter methylation, glioma patients benefit more from treatment with TMZ. […] However, a discordance of MGMT promoter methylation with protein expression was detected in various patient. […] This may be related to the regulation of MGMT protein by Wnt signaling in addition to the regulation of MGMT promoter methylation.

• #54 Glioblastoma: Overview of Disease and Treatment | Oncology Nursing Society

  https://www.ons.org/publications-research/cjon/20/5/supplement-october-2016-glioblastoma-treatment/glioblastoma

  An analysis by Johnson and ONeill (2012) demonstrated a statistically significant improvement in OS since the onset of aggressive multimodality treatment. […] The analysis of this trial also led to the identification of another strong predictor of patient-related outcomes: the methylation of the MGMT gene, located on chromosome 10q26. […] Patients who have methylated (not activated) MGMT exhibit compromised DNA repair. […] Therefore, the expression of methylated MGMT is beneficial for patients undergoing TMZ chemotherapy and RT. […] Despite maximal initial resection and multimodality therapy, about 70% of GBM patients will experience disease progression within one year of diagnosis. […] Re-resection is an option for some patients, and surgical debulking can alleviate mass effect and symptoms, such as seizures, speech, and motor deficits, frequently seen at recurrence.

• #55 Issues Related to the Study of Malignant Brain Tumors

  https://www.barrowneuro.org/for-physicians-researchers/education/grand-rounds-publications-media/barrow-quarterly/volume-14-no-2-1998/issues-related-study-malignant-brain-tumors/

  In brain tumors, genomic instability appears to be more important to progression rather than to the initiation of a tumor. […] The concept that tumors progress to a more malignant state by the acquisition of mutations is not new. […] The mechanisms underlying this genetic variability are areas of intense research. […] In gliomas, telomerase is seldom amplified although about 60% of gliomas show alterations in telomeric length. […] A breakdown in any one of these mechanisms has been attributed to genomic instability. […] Two general categories of genes are directly involved in transformation and progression of the malignant process by one or more of the mechanisms described above. Oncogenes are genes capable of transforming a eukaryotic cell into a cell that grows in a manner analogous to tumor cells, while tumor suppressor genes are genes capable of suppressing tumor formation.

• #56 Long Non-Coding RNAs in Malignant Human Brain Tumors: Driving Forces Behind Progression and Therapy

  https://www.mdpi.com/1422-0067/26/2/694

  Long non-coding RNAs (lncRNAs) play a pivotal role in regulating gene expression and are critically involved in the progression of malignant brain tumors, including glioblastoma, medulloblastoma, and meningioma. […] This review highlights the multifaceted impact of lncRNA dysregulation on tumor progression and underscores their potential as therapeutic targets to enhance the efficacy of chemotherapy, radiotherapy, and immunotherapy. […] Given the strong correlation between lncRNA dysregulation and cancer progression, lncRNAs have emerged as valuable molecular biomarkers for diagnosis, prognosis, and potential therapeutic targets. […] Malignant brain tumors present significant health challenges due to their low survival rates and limited therapeutic options, particularly glioblastoma (GB), medulloblastoma (MB), and meningioma, which affect both adults and children.

• #57 Long Non-Coding RNAs in Malignant Human Brain Tumors: Driving Forces Behind Progression and Therapy

  https://www.mdpi.com/1422-0067/26/2/694

  LncRNAs regulate radiotherapy responses by modulating key signaling pathways. […] LncRNAs play critical roles in a variety of cellular processes, including tumor cell proliferation, migration, invasion, epithelial–mesenchymal transition (EMT), apoptosis, metabolism, immunity, and ferroptosis, all of which can either facilitate or inhibit tumor initiation and progression.

• #58 Long Non-Coding RNAs in Malignant Human Brain Tumors: Driving Forces Behind Progression and Therapy

  https://www.mdpi.com/1422-0067/26/2/694

  Long non-coding RNAs (lncRNAs) play a pivotal role in regulating gene expression and are critically involved in the progression of malignant brain tumors, including glioblastoma, medulloblastoma, and meningioma. […] This review highlights the multifaceted impact of lncRNA dysregulation on tumor progression and underscores their potential as therapeutic targets to enhance the efficacy of chemotherapy, radiotherapy, and immunotherapy. […] Given the strong correlation between lncRNA dysregulation and cancer progression, lncRNAs have emerged as valuable molecular biomarkers for diagnosis, prognosis, and potential therapeutic targets. […] Malignant brain tumors present significant health challenges due to their low survival rates and limited therapeutic options, particularly glioblastoma (GB), medulloblastoma (MB), and meningioma, which affect both adults and children.

• #59 Issues Related to the Study of Malignant Brain Tumors

  https://www.barrowneuro.org/for-physicians-researchers/education/grand-rounds-publications-media/barrow-quarterly/volume-14-no-2-1998/issues-related-study-malignant-brain-tumors/

  In brain tumors, genomic instability appears to be more important to progression rather than to the initiation of a tumor. […] The concept that tumors progress to a more malignant state by the acquisition of mutations is not new. […] The mechanisms underlying this genetic variability are areas of intense research. […] In gliomas, telomerase is seldom amplified although about 60% of gliomas show alterations in telomeric length. […] A breakdown in any one of these mechanisms has been attributed to genomic instability. […] Two general categories of genes are directly involved in transformation and progression of the malignant process by one or more of the mechanisms described above. Oncogenes are genes capable of transforming a eukaryotic cell into a cell that grows in a manner analogous to tumor cells, while tumor suppressor genes are genes capable of suppressing tumor formation.

• #60 Glioblastoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/283252-overview

  One of the histopathologic hallmarks of glioblastoma is microvascular proliferation—the rapid growth of small-lumen, multilayered blood vessels. […] The other defining histopathologic feature of glioblastoma is necrosis, or cell death. […] Of all the astrocytic neoplasms, glioblastomas contain the greatest number of genetic changes. In most cases these result from the accumulation of multiple mutations. […] The TERT gene encodes a reverse transcriptase subunit of telomerase, a ribonucleoprotein responsible for repairing telomeres damaged during cellular replication, thereby maintaining telomere length and preventing cell death. […] Whole chromosome gain (trisomy 7) and whole chromosome 10 loss (monosomy 10) are among the most common numerical chromosome alterations in glioblastoma.

• #61 Glioblastoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/283252-overview

  One of the histopathologic hallmarks of glioblastoma is microvascular proliferation—the rapid growth of small-lumen, multilayered blood vessels. […] The other defining histopathologic feature of glioblastoma is necrosis, or cell death. […] Of all the astrocytic neoplasms, glioblastomas contain the greatest number of genetic changes. In most cases these result from the accumulation of multiple mutations. […] The TERT gene encodes a reverse transcriptase subunit of telomerase, a ribonucleoprotein responsible for repairing telomeres damaged during cellular replication, thereby maintaining telomere length and preventing cell death. […] Whole chromosome gain (trisomy 7) and whole chromosome 10 loss (monosomy 10) are among the most common numerical chromosome alterations in glioblastoma.

• #62 Molecular Determinants of Malignant Brain Cancers: From Intracellular Alterations to Invasion Mediated by Extracellular Vesicles

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5751372/

  Moreover, the rapid proliferation of the malignant cells per se has a metabolic effect on the microenvironment, which is rapidly deprived of glucose and oxygen, becoming acidic and hypoxic. […] These modifications are part of the so called epithelial-mesenchymal transition (EMT), which, although its role in glioma is still controversial, seems to be determinant for the degree of malignancy. […] At the base of invasion and progression of glial tumors there is a continuous interaction between neoplastic cells and ECM. […] A variety of ECM components have been found to be either up- or down-regulated in brain tumors and have been therefore considered as possible key molecules in the mechanism of invasion of malignant glial tumors. […] Glioma cell invasion into the surrounding parenchyma requires, besides modifications of the cell shape and production of invadopodia, also adjustment of cell volume.

• #63 Antioxidants in brain tumors: current therapeutic significance and future prospects | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01668-9

  Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. […] The role of OS in oncogenesis at different phases of tumor development and progression has been investigated. OS develops due to a disproportion between the synthesis and accumulation of the free radicals referred to as ROS and reactive nitrogen species (RNS). […] Several studies have revealed the association between OS and brain tumor development. The brain comprises 2% of the entire body, yet it consumes 20% of total bodys oxygen, representing the possibility of more free radical production compared to other organs.

• #64 Brain Tumor Glossary

  https://braintumor.org/brain-tumors/diagnosis-treatment/diagnosis/brain-tumor-glossary/

  Malignant Brain Tumors contain cancer cells and often do not have clear borders. They are considered to be life-threatening because they grow rapidly and invade surrounding brain tissue. Although malignant brain tumors very rarely spread to other areas of the body, they can spread throughout the brain or to the spine. These tumors can be treated with surgery, chemotherapy and radiation, but they may recur after treatment. […] IDH has three forms, IDH1, IDH2, and IDH3. Mutated forms of IDH1 and IDH2 are often found in gliomas, typically low-grade gliomas and secondary glioblastomas (though IDH1 mutations are occasionally found in primary GBM patients, as well). These mutations, which occur early in the tumor-forming process, change the function of the enzymes, causing them to produce a metabolite called 2-hydroxyglutarate (2HG), instead of a molecule called NADPH. The presence of an IDH mutation in patients tumors is a biomarker for improved prognosis. This means that glioma patients that have an IDH mutation tend to live longer than patients without an IDH mutation (IDH-wide-type). […] Tumorigenesis is the process of transformation of normal cells into tumor cells.

• #65 New therapy for glioma receives FDA approval | Duke Department of Neurosurgery

  https://neurosurgery.duke.edu/news/new-therapy-glioma-receives-fda-approval

  The discovery of the mutant IDH gene is one of the most important discoveries in neuro-oncology. The IDH mutation has been incorporated by the World Health Organization into the rapid and accurate diagnosis and classification of astrocytic, oligodendroglial, and glioblastoma multiforme brain tumors. Never before has there been a single gene mutation that contributed so greatly to classification. Most importantly, it was immediately recognized that the IDH mutation could be targeted with drugs to treat the group of patients that had malignant brain tumors that expressed the IDH mutation. […] Mutations in the IDH1 or IDH2 genes result in elevated levels of the oncometabolite D-2HG, disrupting normal cellular functions and contributing to tumorigenesis. Vorasidenib selectively binds to the mutated IDH1 and IDH2 enzymes, inhibiting their activity and thereby reducing the production of D-2HG. This inhibition helps to restore normal cellular processes, reduce tumor cell proliferation, and promote the differentiation of cancer cells.

• #66 New therapy for glioma receives FDA approval | Duke Department of Neurosurgery

  https://neurosurgery.duke.edu/news/new-therapy-glioma-receives-fda-approval

  The discovery of the mutant IDH gene is one of the most important discoveries in neuro-oncology. The IDH mutation has been incorporated by the World Health Organization into the rapid and accurate diagnosis and classification of astrocytic, oligodendroglial, and glioblastoma multiforme brain tumors. Never before has there been a single gene mutation that contributed so greatly to classification. Most importantly, it was immediately recognized that the IDH mutation could be targeted with drugs to treat the group of patients that had malignant brain tumors that expressed the IDH mutation. […] Mutations in the IDH1 or IDH2 genes result in elevated levels of the oncometabolite D-2HG, disrupting normal cellular functions and contributing to tumorigenesis. Vorasidenib selectively binds to the mutated IDH1 and IDH2 enzymes, inhibiting their activity and thereby reducing the production of D-2HG. This inhibition helps to restore normal cellular processes, reduce tumor cell proliferation, and promote the differentiation of cancer cells.

• #67 Frontiers | Iron Transporters and Ferroptosis in Malignant Brain Tumors

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.861834/full

  Malignant brain tumors represent approximately 1.5% of all malignant tumors. The survival rate among patients is relatively low and the mortality rate of pediatric brain tumors ranks first among all childhood malignant tumors. At present malignant brain tumors remain incurable. Although some tumors can be treated with surgery and chemotherapy, new treatment strategies are urgent owing to the poor clinical prognosis. Iron is an essential trace element in many biological processes of the human body. Iron transporters play a crucial role in iron absorption and transport. Ferroptosis, an iron-dependent form of nonapoptotic cell death, is characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS) derived from iron metabolism. Recently, compelling evidence has shown that inducing ferroptosis of tumor cells is a potential therapeutic strategy.

• #68 Frontiers | Iron Transporters and Ferroptosis in Malignant Brain Tumors

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.861834/full

  Ferroptosis is a form of iron-dependent regulatory cell death distinguished from necrosis, apoptosis and autophagy, which can be triggered by the small-molecule compound erastin and RSL3. Iron and polyunsaturated fatty acids (PUFAs) act as raw materials for lipid peroxidation to promote the occurrence of ferroptosis. […] Ferroptosis plays a key role in the development of malignant brain tumors. As an important part of ferroptosis, relevant transporters can regulate amino acid metabolism and iron metabolism and are essential for the maintenance of iron homeostasis. Disorders of iron homeostasis in the brain will increase the risk of tumors, which may be one of the factors leading to the increased incidence of brain tumors. […] Inducing ferroptosis of tumor cells is a newly discovered strategy for the treatment of malignant brain tumors, but many problems remain to be solved, including elucidating the mechanism of ferroptosis in different malignant brain tumors, discovering new therapeutic targets for inducing ferroptosis of tumor cells, and increasing the tumor cell targeting of ferroptosis inducers.

• #69 Antioxidants in brain tumors: current therapeutic significance and future prospects | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01668-9

  Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. […] The role of OS in oncogenesis at different phases of tumor development and progression has been investigated. OS develops due to a disproportion between the synthesis and accumulation of the free radicals referred to as ROS and reactive nitrogen species (RNS). […] Several studies have revealed the association between OS and brain tumor development. The brain comprises 2% of the entire body, yet it consumes 20% of total bodys oxygen, representing the possibility of more free radical production compared to other organs.

• #70 Antioxidants in brain tumors: current therapeutic significance and future prospects | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01668-9

  Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. […] The role of OS in oncogenesis at different phases of tumor development and progression has been investigated. OS develops due to a disproportion between the synthesis and accumulation of the free radicals referred to as ROS and reactive nitrogen species (RNS). […] Several studies have revealed the association between OS and brain tumor development. The brain comprises 2% of the entire body, yet it consumes 20% of total bodys oxygen, representing the possibility of more free radical production compared to other organs.

• #71 Antioxidants in brain tumors: current therapeutic significance and future prospects | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01668-9

  Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. […] The role of OS in oncogenesis at different phases of tumor development and progression has been investigated. OS develops due to a disproportion between the synthesis and accumulation of the free radicals referred to as ROS and reactive nitrogen species (RNS). […] Several studies have revealed the association between OS and brain tumor development. The brain comprises 2% of the entire body, yet it consumes 20% of total bodys oxygen, representing the possibility of more free radical production compared to other organs.

• #72 Antioxidants in brain tumors: current therapeutic significance and future prospects | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01668-9

  The role of antioxidants on metabolic reprogramming and their influence on downstream signaling events induced by tumor suppressor gene mutations are critically discussed. […] The requirements of pro- and antioxidant effects of exogenous antioxidants in brain tumor treatment under different conditions are critically discussed along with the reasons behind the conflicting outcomes in different reports. […] Thus, the precise role of antioxidants in chemoprevention is still unclear. Exogenous antioxidants also support prooxidant chemistry that is associated with the killing of cancer cells by induction of ROS in excess. […] The therapeutic dose determines whether effects rendered will be pro- or antioxidant. It is thought that exogenous antioxidants may be helpful for chemotherapeutic purposes at pharmacological/high doses, however dietary amounts may be more useful as chemoprevention.

• #73 Antioxidants in brain tumors: current therapeutic significance and future prospects | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01668-9

  Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. […] The role of OS in oncogenesis at different phases of tumor development and progression has been investigated. OS develops due to a disproportion between the synthesis and accumulation of the free radicals referred to as ROS and reactive nitrogen species (RNS). […] Several studies have revealed the association between OS and brain tumor development. The brain comprises 2% of the entire body, yet it consumes 20% of total bodys oxygen, representing the possibility of more free radical production compared to other organs.

• #74 Antioxidants in brain tumors: current therapeutic significance and future prospects | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01668-9

  The inclusion of dietary antioxidants following standard cancer treatments often prolongs the life span of glioma patients. That may be attributed to the retardation of tumor recurrence through the chemopreventive role of antioxidants mediated through an antioxidant mechanism. […] Antioxidants negatively influence cancer initiation by endorsing DNA repair. Increasing antioxidant intake has been shown to deplete OS, accordingly, creating an energy crisis for preneoplastic cells, resulting in suppression of cell growth and activation of cell death pathways to impart chemopreventive effect during cancer progression pathway. […] Thus, antioxidants may exhibit a chemopreventive role by restoring PTEN activities. Mutation of PTEN gene is evident in glioblastoma cells. […] Thus, antioxidants surely can hinder oncogenesis by restoring redox balance, preventing DNA damage, regulating DNA methylation status, and repairing damaged DNA.

• #75 Antioxidants in brain tumors: current therapeutic significance and future prospects | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01668-9

  The role of antioxidants on metabolic reprogramming and their influence on downstream signaling events induced by tumor suppressor gene mutations are critically discussed. […] The requirements of pro- and antioxidant effects of exogenous antioxidants in brain tumor treatment under different conditions are critically discussed along with the reasons behind the conflicting outcomes in different reports. […] Thus, the precise role of antioxidants in chemoprevention is still unclear. Exogenous antioxidants also support prooxidant chemistry that is associated with the killing of cancer cells by induction of ROS in excess. […] The therapeutic dose determines whether effects rendered will be pro- or antioxidant. It is thought that exogenous antioxidants may be helpful for chemotherapeutic purposes at pharmacological/high doses, however dietary amounts may be more useful as chemoprevention.

• #76 Glioblastoma Multiforme – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558954/

  Glioblastoma multiforme (GBM) is the most malignant and pervasive subtype of glioma and is the most common primary brain tumor in adults. […] The only well-established causative factor is exposure to high doses of ionizing radiation. […] GBM shows features of immune escape and high tumor heterogeneity. Moreover, the relative immune privileged milieu owing to the lack of antigen-presenting cells (APCs) and lymphatics within the CNS further contributes to the poor prognosis among cohorts with GBM. […] Malignant cells have abnormal proliferation, growth, and angiogenesis due to mutations. […] GBM is found to have many genetic and epigenetic mutations. The mutations are essential to identify and classify to understand the tumor behavior and treatment resistance throughout the clinical course.

• #77 Glioblastoma Multiforme – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558954/

  Due to different triggering mutations and critical mutations in the GBM stem cells, GBM is classified into primary tumors arising from neural stem cell precursors and secondary tumors arising from mutations in mature neural cells like astrocytes. […] Alteration in genetic information, causing expression and suppression of genes compared to their physiological levels in healthy brain cells, leads to cellular and extracellular matrix changes, resulting in a multiform number of biochemical forms. […] The definitive diagnosis is made through a histopathological examination that reveals poorly differentiated pleomorphic cells with predominant astrocytic differentiation. High mitotic activity, microvascular proliferation, and necrosis are hallmark features of GBM. […] The only well-established causative factor implicated in GBM is exposure to high doses of ionizing radiation. […] GBM shows immune escape features and high tumor heterogeneity. […] Malignant cells have abnormal proliferation, growth, and angiogenesis due to mutations. […] The definitive diagnosis is through a histopathological examination.

• #78 ADAR1 inhibition: Hijacking an innate immune mechanism present in all malignant cells | The Brain Tumour Charity Research Project

  https://www.thebraintumourcharity.org/brain-tumour-diagnosis-treatment/types-of-brain-tumour-adult/glioblastoma/glioblastoma-research/hijacking-innate-immune-mechanism-in-malignant-cells/

  Glioblastomas are incurable brain tumours. […] New therapeutic strategies have instead advanced towards exploiting the immune system to fight glioblastoma tumours. […] The hypothesis is that getting rid of ADAR1 in cancer cells would confound cancer cells defence mechanisms. […] The lost ability to recognise molecules produced during normal physiological processes would lead to an increase vulnerability of cancer cells. […] The tumour microenvironment (TME) around glioblastoma cells is often highly immunosuppressive. […] By reprogramming the immune microenvironment to fight cancer cells, TME-targeted immunotherapies could overcome the immunosuppressive nature of the microenvironment and enhance the effectiveness of ADAR1 inhibition. […] Dr lvarez-Prados project is critical in developing new therapeutic approaches that simultaneously target cancer cells and their supporting microenvironment. […] This project could lead to more effective treatment for patients, by simultaneously attacking cancer cells from the inside and outside, and would be less toxic, as it exploits a vulnerability present within glioblastoma cells.

• #79 New mRNA cancer vaccine triggers fierce immune response to fight malignant brain tumor – UF Health

  https://ufhealth.org/news/2024/uf-developed-mrna-vaccine-triggers-fierce-immune-response-to-fight-malignant-brain-tumor

  In a first-ever human clinical trial of four adult patients, an mRNA cancer vaccine developed at UF quickly reprogrammed the immune system to attack glioblastoma, the most aggressive and lethal brain tumor. […] The breakthrough now will be tested in a Phase 1 pediatric clinical trial for brain cancer. […] The new publication is the culmination of promising translational results over seven years of studies, starting in preclinical mouse models and then in a clinical trial of 10 pet dogs that had spontaneously developed terminal brain cancer and had no other treatment options. […] After treating pet dogs that had spontaneously developed brain cancer with personalized mRNA vaccines, Sayour’s team advanced the research to a small Food and Drug Administration-approved clinical trial designed to ensure safety and test feasibility before expanding to a larger trial.

• #80 Cancers | Special Issue : Resistance Mechanisms in Malignant Brain Tumors

  https://www.mdpi.com/journal/cancers/special_issues/Resistance_Mechanism_Malignant_Brain_Tumor

  Tumor microenvironment effects mediated by the complex crosstalk between tumor and non-malignant cells including astrocytes, neurons, vasculature (endothelial cells and pericytes), as well as distinct immune compartment of the brain comprising microglia, resident and blood-recruited macrophages and lymphocytes. […] Microanatomical and biomechanical features of the tumor itself, such as the inefficient drug delivery, hypoxia and acidosis, tumor infiltration and invasion, vessel co-option and angiogenesis. […] This Special Issue will focus on the tumor features and mechanisms that convey resistance to therapy in malignant brain tumors.

• #81 Signaling pathways in brain tumors and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01260-z

  The production of R-2HG makes IDH mutant cells sensitive to alkylating agents. […] The clinically significant bifunctional alkylating agents procarbazine and CCNU/lomustine induces highly genotoxic DNA interstrand crosslinks, and are a part of the PCV chemotherapeutic regimen successfully utilized in combination with radiotherapy for the treatment of brain tumors with IDH mutation status. […] The vascular endothelial growth factor receptor (VEGFR) signaling pathway has been considered a key factor in GBM tumor survival. […] Bevacizumab inhibits angiogenesis by acting as a humanized monoclonal antibody against the VEGF-A ligand. […] The transforming growth factor beta (TGF-) protein family has complicated functions in diverse regulatory pathways, where TGF-2 is a T cell inhibitor in the GBM tumor microenvironment that is found in approximately 90% of GBM tumor cells. […] The above crucial signaling pathways involved in glioma were demonstrated in Fig. 2.

• #82 Glioblastoma Multiforme – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558954/

  Glioblastoma multiforme (GBM) is the most malignant and pervasive subtype of glioma and is the most common primary brain tumor in adults. […] The only well-established causative factor is exposure to high doses of ionizing radiation. […] GBM shows features of immune escape and high tumor heterogeneity. Moreover, the relative immune privileged milieu owing to the lack of antigen-presenting cells (APCs) and lymphatics within the CNS further contributes to the poor prognosis among cohorts with GBM. […] Malignant cells have abnormal proliferation, growth, and angiogenesis due to mutations. […] GBM is found to have many genetic and epigenetic mutations. The mutations are essential to identify and classify to understand the tumor behavior and treatment resistance throughout the clinical course.

• #83 Glioblastoma Multiforme – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558954/

  Glioblastoma multiforme (GBM) is the most malignant and pervasive subtype of glioma and is the most common primary brain tumor in adults. […] The only well-established causative factor is exposure to high doses of ionizing radiation. […] GBM shows features of immune escape and high tumor heterogeneity. Moreover, the relative immune privileged milieu owing to the lack of antigen-presenting cells (APCs) and lymphatics within the CNS further contributes to the poor prognosis among cohorts with GBM. […] Malignant cells have abnormal proliferation, growth, and angiogenesis due to mutations. […] GBM is found to have many genetic and epigenetic mutations. The mutations are essential to identify and classify to understand the tumor behavior and treatment resistance throughout the clinical course.

• #84 ADAR1 inhibition: Hijacking an innate immune mechanism present in all malignant cells | The Brain Tumour Charity Research Project

  https://www.thebraintumourcharity.org/brain-tumour-diagnosis-treatment/types-of-brain-tumour-adult/glioblastoma/glioblastoma-research/hijacking-innate-immune-mechanism-in-malignant-cells/

  Glioblastomas are incurable brain tumours. […] New therapeutic strategies have instead advanced towards exploiting the immune system to fight glioblastoma tumours. […] The hypothesis is that getting rid of ADAR1 in cancer cells would confound cancer cells defence mechanisms. […] The lost ability to recognise molecules produced during normal physiological processes would lead to an increase vulnerability of cancer cells. […] The tumour microenvironment (TME) around glioblastoma cells is often highly immunosuppressive. […] By reprogramming the immune microenvironment to fight cancer cells, TME-targeted immunotherapies could overcome the immunosuppressive nature of the microenvironment and enhance the effectiveness of ADAR1 inhibition. […] Dr lvarez-Prados project is critical in developing new therapeutic approaches that simultaneously target cancer cells and their supporting microenvironment. […] This project could lead to more effective treatment for patients, by simultaneously attacking cancer cells from the inside and outside, and would be less toxic, as it exploits a vulnerability present within glioblastoma cells.

• #85 New mRNA cancer vaccine triggers fierce immune response to fight malignant brain tumor – UF Health

  https://ufhealth.org/news/2024/uf-developed-mrna-vaccine-triggers-fierce-immune-response-to-fight-malignant-brain-tumor

  In a first-ever human clinical trial of four adult patients, an mRNA cancer vaccine developed at UF quickly reprogrammed the immune system to attack glioblastoma, the most aggressive and lethal brain tumor. […] The breakthrough now will be tested in a Phase 1 pediatric clinical trial for brain cancer. […] The new publication is the culmination of promising translational results over seven years of studies, starting in preclinical mouse models and then in a clinical trial of 10 pet dogs that had spontaneously developed terminal brain cancer and had no other treatment options. […] After treating pet dogs that had spontaneously developed brain cancer with personalized mRNA vaccines, Sayour’s team advanced the research to a small Food and Drug Administration-approved clinical trial designed to ensure safety and test feasibility before expanding to a larger trial.

• #86 New mRNA cancer vaccine triggers fierce immune response to fight malignant brain tumor – UF Health

  https://ufhealth.org/news/2024/uf-developed-mrna-vaccine-triggers-fierce-immune-response-to-fight-malignant-brain-tumor

  In a first-ever human clinical trial of four adult patients, an mRNA cancer vaccine developed at UF quickly reprogrammed the immune system to attack glioblastoma, the most aggressive and lethal brain tumor. […] The breakthrough now will be tested in a Phase 1 pediatric clinical trial for brain cancer. […] The new publication is the culmination of promising translational results over seven years of studies, starting in preclinical mouse models and then in a clinical trial of 10 pet dogs that had spontaneously developed terminal brain cancer and had no other treatment options. […] After treating pet dogs that had spontaneously developed brain cancer with personalized mRNA vaccines, Sayour’s team advanced the research to a small Food and Drug Administration-approved clinical trial designed to ensure safety and test feasibility before expanding to a larger trial.

• #87 New mRNA cancer vaccine triggers fierce immune response to fight malignant brain tumor – UF Health

  https://ufhealth.org/news/2024/uf-developed-mrna-vaccine-triggers-fierce-immune-response-to-fight-malignant-brain-tumor

  The demonstration that making an mRNA cancer vaccine in this fashion generates similar and strong responses across mice, pet dogs that have developed cancer spontaneously and human patients with brain cancer is a really important finding. […] While too early in the trial to assess the clinical effects of the vaccine, the patients either lived disease-free longer than expected or survived longer than expected. […] The next step, through support from the Food and Drug Administration and the CureSearch for Children’s Cancer foundation, will be an expanded Phase I clinical trial to include up to 24 adult and pediatric patients to validate the findings. […] I am hopeful that this could be a new paradigm for how we treat patients, a new platform technology for how we can modulate the immune system.

• #88 Brain Tumors – AANS

  https://www.aans.org/patients/conditions-treatments/brain-tumors/

  Once a cell is dividing rapidly and internal mechanisms to check its growth are damaged, the cell can eventually grow into a tumor. Another line of defense may be the body’s immune system, which optimally would detect the abnormal cell and kill it. Tumors may produce substances that block the immune system from recognizing the abnormal tumor cells and eventually overpower all internal and external deterrents to its growth. […] A rapidly growing tumor may need more oxygen and nutrients than can be provided by the local blood supply intended for normal tissue. Tumors can produce substances called angiogenesis factors that promote the growth of blood vessels. The new vessels that grow increase the supply of nutrients to the tumor, and, eventually, the tumor becomes dependent on these new vessels. Research is being done in this area, but more extensive research is necessary to translate this knowledge into potential therapies.

• #89 Glioblastoma Multiforme – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558954/

  Glioblastoma multiforme (GBM) is the most malignant and pervasive subtype of glioma and is the most common primary brain tumor in adults. […] The only well-established causative factor is exposure to high doses of ionizing radiation. […] GBM shows features of immune escape and high tumor heterogeneity. Moreover, the relative immune privileged milieu owing to the lack of antigen-presenting cells (APCs) and lymphatics within the CNS further contributes to the poor prognosis among cohorts with GBM. […] Malignant cells have abnormal proliferation, growth, and angiogenesis due to mutations. […] GBM is found to have many genetic and epigenetic mutations. The mutations are essential to identify and classify to understand the tumor behavior and treatment resistance throughout the clinical course.

• #90 Signaling pathways in brain tumors and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01260-z

  The production of R-2HG makes IDH mutant cells sensitive to alkylating agents. […] The clinically significant bifunctional alkylating agents procarbazine and CCNU/lomustine induces highly genotoxic DNA interstrand crosslinks, and are a part of the PCV chemotherapeutic regimen successfully utilized in combination with radiotherapy for the treatment of brain tumors with IDH mutation status. […] The vascular endothelial growth factor receptor (VEGFR) signaling pathway has been considered a key factor in GBM tumor survival. […] Bevacizumab inhibits angiogenesis by acting as a humanized monoclonal antibody against the VEGF-A ligand. […] The transforming growth factor beta (TGF-) protein family has complicated functions in diverse regulatory pathways, where TGF-2 is a T cell inhibitor in the GBM tumor microenvironment that is found in approximately 90% of GBM tumor cells. […] The above crucial signaling pathways involved in glioma were demonstrated in Fig. 2.

• #91 Patient education: High-grade glioma in adults (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-grade-glioma-in-adults-beyond-the-basics

  Gliomas cause symptoms by invading (growing) into and/or creating pressure in nearby normal brain tissue. […] Treatment of a high-grade glioma includes measures to relieve symptoms and eliminate or control the tumor. […] Because there are not curative treatments for most types of high-grade glioma, many people are encouraged to participate in a clinical trial, if possible. […] Radiation therapy uses high-energy x-rays to kill cancer cells and is usually recommended following surgery to kill any remaining tumor cells. […] Bevacizumab (Brand name: Avastin) is an antibody (a type of protein) that targets a protein called vascular endothelial growth factor (VEGF). VEGF causes a growing cancer to develop its own blood supply, which is essential for the tumor to grow and spread. Bevacizumab disrupts the process of new blood vessel formation, thereby depriving the tumor of its supply of nutrients.

• #92 Signaling pathways in brain tumors and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01260-z

  The production of R-2HG makes IDH mutant cells sensitive to alkylating agents. […] The clinically significant bifunctional alkylating agents procarbazine and CCNU/lomustine induces highly genotoxic DNA interstrand crosslinks, and are a part of the PCV chemotherapeutic regimen successfully utilized in combination with radiotherapy for the treatment of brain tumors with IDH mutation status. […] The vascular endothelial growth factor receptor (VEGFR) signaling pathway has been considered a key factor in GBM tumor survival. […] Bevacizumab inhibits angiogenesis by acting as a humanized monoclonal antibody against the VEGF-A ligand. […] The transforming growth factor beta (TGF-) protein family has complicated functions in diverse regulatory pathways, where TGF-2 is a T cell inhibitor in the GBM tumor microenvironment that is found in approximately 90% of GBM tumor cells. […] The above crucial signaling pathways involved in glioma were demonstrated in Fig. 2.

• #93 Patient education: High-grade glioma in adults (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-grade-glioma-in-adults-beyond-the-basics

  Gliomas cause symptoms by invading (growing) into and/or creating pressure in nearby normal brain tissue. […] Treatment of a high-grade glioma includes measures to relieve symptoms and eliminate or control the tumor. […] Because there are not curative treatments for most types of high-grade glioma, many people are encouraged to participate in a clinical trial, if possible. […] Radiation therapy uses high-energy x-rays to kill cancer cells and is usually recommended following surgery to kill any remaining tumor cells. […] Bevacizumab (Brand name: Avastin) is an antibody (a type of protein) that targets a protein called vascular endothelial growth factor (VEGF). VEGF causes a growing cancer to develop its own blood supply, which is essential for the tumor to grow and spread. Bevacizumab disrupts the process of new blood vessel formation, thereby depriving the tumor of its supply of nutrients.

• #94 Brain Neoplasms: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/779664-overview

  Tumors of the brain produce neurologic manifestations through a number of mechanisms. Small, critically located tumors may damage specific neural pathways traversing the brain. Tumors can invade, infiltrate, or supplant normal parenchymal tissue, disrupting normal function. Because the brain dwells in the limited volume of the cranial vault, growth of intracranial tumors with accompanying edema may cause increased intracranial pressure. Tumors adjacent to the third and fourth ventricles may impede the flow of cerebrospinal fluid, leading to obstructive hydrocephalus. In addition, tumors generate new blood vessels (ie, angiogenesis), disrupting the normal blood-brain barrier and promoting edema. […] The cumulative effects of tumor invasion, edema, and hydrocephalus may elevate the intracranial pressure (ICP) and impair cerebral perfusion. Intracranial compartmental rise in ICP may provoke shifting or herniation of tissue under the falx cerebri, through the tentorium cerebelli, or through the foramen magnum.

• #95 Overview of Intracranial Tumors – Neurologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/neurologic-disorders/intracranial-and-spinal-tumors/overview-of-intracranial-tumors

  A malignant tumor can develop new internal blood vessels, which can bleed or become occluded, resulting in necrosis and neurologic dysfunction that mimics stroke. […] Malignant primary tumors grow rapidly but rarely spread beyond the CNS. Death results from local tumor growth and/or tumor-related hemorrhage and thus can result from benign as well as malignant tumors. […] Deterioration in mental status is the second most common symptom. Manifestations include drowsiness, lethargy, personality changes, disordered conduct, and impaired cognition, particularly with malignant brain tumors. […] Treatment of metastatic tumors includes radiation therapy, which can be delivered as whole-brain or conformal stereotactic radiosurgery.

• #96 Glioblastoma Multiforme – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558954/

  Glioblastoma multiforme (GBM) is the most malignant and pervasive subtype of glioma and is the most common primary brain tumor in adults. […] The only well-established causative factor is exposure to high doses of ionizing radiation. […] GBM shows features of immune escape and high tumor heterogeneity. Moreover, the relative immune privileged milieu owing to the lack of antigen-presenting cells (APCs) and lymphatics within the CNS further contributes to the poor prognosis among cohorts with GBM. […] Malignant cells have abnormal proliferation, growth, and angiogenesis due to mutations. […] GBM is found to have many genetic and epigenetic mutations. The mutations are essential to identify and classify to understand the tumor behavior and treatment resistance throughout the clinical course.

• #97 Glioblastoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/283252-overview

  Glioblastoma (GBM), formerly known as glioblastoma multiforme, is the most common and malignant of adult gliomas. Gliomas are primary neoplasms of the central nervous system that arise from glial cells or their progenitors. […] The etiology of GBM is unknown in most cases. Suggested causes include the following: Genetic factors; Exposure to ionizing radiation; Exposure to non-ionizing radiation; Head injury, N-nitroso compounds, occupational hazards, electromagnetic field exposure (all inconclusive). […] Because GBM is now a molecular diagnosis, genetic studies for IDH and H3 status are essential, and genetic studies for TERT promoter mutation, EGFR gene amplification, and +7/-10 chromosome copy number changes are important as well. Tumor genetics are also useful for predicting response to adjuvant therapy.

• #98 Glioblastoma Multiforme – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558954/

  Due to different triggering mutations and critical mutations in the GBM stem cells, GBM is classified into primary tumors arising from neural stem cell precursors and secondary tumors arising from mutations in mature neural cells like astrocytes. […] Alteration in genetic information, causing expression and suppression of genes compared to their physiological levels in healthy brain cells, leads to cellular and extracellular matrix changes, resulting in a multiform number of biochemical forms. […] The definitive diagnosis is made through a histopathological examination that reveals poorly differentiated pleomorphic cells with predominant astrocytic differentiation. High mitotic activity, microvascular proliferation, and necrosis are hallmark features of GBM. […] The only well-established causative factor implicated in GBM is exposure to high doses of ionizing radiation. […] GBM shows immune escape features and high tumor heterogeneity. […] Malignant cells have abnormal proliferation, growth, and angiogenesis due to mutations. […] The definitive diagnosis is through a histopathological examination.

• #99 Neuro-ophthalmic Manifestations of Glioblastoma Multiforme – EyeWiki

  https://eyewiki.org/Neuro-ophthalmic_Manifestations_of_Glioblastoma_Multiforme

  Glioblastoma multiforme (GBM) is a Grade IV astrocytoma and represents the most common primary malignant brain tumor in adults. […] In general, gliomas undergo malignant transformation through the sequential accumulation of genetic mutations and abnormal regulation of growth factor signaling pathways. […] GBM has two clinical forms primary and secondary GBM. Primary GBM usually arises de novo and often has amplified, mutated epidermal-growth factor receptor (EGFR), whereas secondary GBM arises from prior low-grade astrocytoma and often has increased platelet-derived growth factor A (PDGF-A) receptor signaling. […] Even though primary and secondary GBM have different mutations in their pathogenesis, they both result in aberrations in the same signaling pathways, ultimately resulting in increased cell proliferation, inhibition of apoptosis, invasion, and angiogenesis.

• #100 Neuro-ophthalmic Manifestations of Glioblastoma Multiforme – EyeWiki

  https://eyewiki.org/Neuro-ophthalmic_Manifestations_of_Glioblastoma_Multiforme

  Glioblastoma multiforme (GBM) is a Grade IV astrocytoma and represents the most common primary malignant brain tumor in adults. […] In general, gliomas undergo malignant transformation through the sequential accumulation of genetic mutations and abnormal regulation of growth factor signaling pathways. […] GBM has two clinical forms primary and secondary GBM. Primary GBM usually arises de novo and often has amplified, mutated epidermal-growth factor receptor (EGFR), whereas secondary GBM arises from prior low-grade astrocytoma and often has increased platelet-derived growth factor A (PDGF-A) receptor signaling. […] Even though primary and secondary GBM have different mutations in their pathogenesis, they both result in aberrations in the same signaling pathways, ultimately resulting in increased cell proliferation, inhibition of apoptosis, invasion, and angiogenesis.

• #101 Neuro-ophthalmic Manifestations of Glioblastoma Multiforme – EyeWiki

  https://eyewiki.org/Neuro-ophthalmic_Manifestations_of_Glioblastoma_Multiforme

  Glioblastoma multiforme (GBM) is a Grade IV astrocytoma and represents the most common primary malignant brain tumor in adults. […] In general, gliomas undergo malignant transformation through the sequential accumulation of genetic mutations and abnormal regulation of growth factor signaling pathways. […] GBM has two clinical forms primary and secondary GBM. Primary GBM usually arises de novo and often has amplified, mutated epidermal-growth factor receptor (EGFR), whereas secondary GBM arises from prior low-grade astrocytoma and often has increased platelet-derived growth factor A (PDGF-A) receptor signaling. […] Even though primary and secondary GBM have different mutations in their pathogenesis, they both result in aberrations in the same signaling pathways, ultimately resulting in increased cell proliferation, inhibition of apoptosis, invasion, and angiogenesis.

• #102 Autophagy in cancers including brain tumors: role of MicroRNAs | Cell Communication and Signaling | Full Text

  https://biosignaling.biomedcentral.com/articles/10.1186/s12964-020-00587-w

  The most frequent genetic alterations/mutations found in gliomas are: hemizygous/homozygous deletion of NF-1 and PTEN; EGFR vIII mutant expression; and EGFR amplification. […] The abnormal signaling resulting from such mutations interacts with PI3K-Akt-mTOR pathways that promotes chemo-resistance and survival in gliomas. […] The Cancer Genome Atlas consortium categorized glioblastoma (GBM) tumors into four molecular sub-types, including neural, classical, mesenchymal, and proneural. […] The particular role of autophagy in contributing to cell death or cell survival in different therapeutic approaches is yet to be fully explained, and a better understanding of these contrary findings is essential to design potential combination therapies. […] MiR-93 modulated autophagy functions in GSCs by synchronized suppression of several autophagy modulators, such as SQSTM1/p62, ATG4B, ATG5 and BECN1/beclin 1.

• #103 Signaling pathways in brain tumors and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01260-z

  Grading using Arabic numerals is recommended, as highlighted by WHO CNS5. […] GBM accounts for 57% of all gliomas while 48% of primary CNS malignancies in HGG, have a median survival time of fewer than 2 years. […] O6 methylguanine DNA methyltransferase (MGMT) is a repair protein that is encoded by the MGMT gene, which can reverse DNA alkylation by depleting itself. […] In patients with MGMT promoter methylation found in 30-50% of isocitrate dehydrogenase (IDH)-wt GBM, gene promoter methylation would repress the expression of this gene. […] Therefore, with MGMT promoter methylation, glioma patients benefit more from treatment with TMZ. […] However, a discordance of MGMT promoter methylation with protein expression was detected in various patient. […] This may be related to the regulation of MGMT protein by Wnt signaling in addition to the regulation of MGMT promoter methylation.

• #104 Glioblastoma Multiforme – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558954/

  Due to different triggering mutations and critical mutations in the GBM stem cells, GBM is classified into primary tumors arising from neural stem cell precursors and secondary tumors arising from mutations in mature neural cells like astrocytes. […] Alteration in genetic information, causing expression and suppression of genes compared to their physiological levels in healthy brain cells, leads to cellular and extracellular matrix changes, resulting in a multiform number of biochemical forms. […] The definitive diagnosis is made through a histopathological examination that reveals poorly differentiated pleomorphic cells with predominant astrocytic differentiation. High mitotic activity, microvascular proliferation, and necrosis are hallmark features of GBM. […] The only well-established causative factor implicated in GBM is exposure to high doses of ionizing radiation. […] GBM shows immune escape features and high tumor heterogeneity. […] Malignant cells have abnormal proliferation, growth, and angiogenesis due to mutations. […] The definitive diagnosis is through a histopathological examination.

• #105 Glioblastoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/283252-overview

  One of the histopathologic hallmarks of glioblastoma is microvascular proliferation—the rapid growth of small-lumen, multilayered blood vessels. […] The other defining histopathologic feature of glioblastoma is necrosis, or cell death. […] Of all the astrocytic neoplasms, glioblastomas contain the greatest number of genetic changes. In most cases these result from the accumulation of multiple mutations. […] The TERT gene encodes a reverse transcriptase subunit of telomerase, a ribonucleoprotein responsible for repairing telomeres damaged during cellular replication, thereby maintaining telomere length and preventing cell death. […] Whole chromosome gain (trisomy 7) and whole chromosome 10 loss (monosomy 10) are among the most common numerical chromosome alterations in glioblastoma.

• #106 Glioblastoma Multiforme – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558954/

  Due to different triggering mutations and critical mutations in the GBM stem cells, GBM is classified into primary tumors arising from neural stem cell precursors and secondary tumors arising from mutations in mature neural cells like astrocytes. […] Alteration in genetic information, causing expression and suppression of genes compared to their physiological levels in healthy brain cells, leads to cellular and extracellular matrix changes, resulting in a multiform number of biochemical forms. […] The definitive diagnosis is made through a histopathological examination that reveals poorly differentiated pleomorphic cells with predominant astrocytic differentiation. High mitotic activity, microvascular proliferation, and necrosis are hallmark features of GBM. […] The only well-established causative factor implicated in GBM is exposure to high doses of ionizing radiation. […] GBM shows immune escape features and high tumor heterogeneity. […] Malignant cells have abnormal proliferation, growth, and angiogenesis due to mutations. […] The definitive diagnosis is through a histopathological examination.

• #107 Patient education: High-grade glioma in adults (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-grade-glioma-in-adults-beyond-the-basics

  Primary brain tumors mainly develop from glial cells. Glial cells provide the structural backbone of the brain and support the function of the neurons (nerve cells), which are responsible for thought, sensation, muscle control, and coordination. […] The term malignant or high-grade glioma refers to tumors that are classified as: Grade 3 (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic ependymoma) and Grade 4 (glioblastoma). […] Astrocytomas, oligodendrogliomas, and glioblastomas are further classified based on whether they have a genetic change in the isocitrate dehydrogenase (IDH) gene. If there is a mutation, the tumor is designated as IDH mutant, and if there is no mutation, the tumor is designated as IDH wildtype. IDH-wildtype tumors are more aggressive and behave like high-grade glioma.

• #108 Patient education: High-grade glioma in adults (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-grade-glioma-in-adults-beyond-the-basics

  Primary brain tumors mainly develop from glial cells. Glial cells provide the structural backbone of the brain and support the function of the neurons (nerve cells), which are responsible for thought, sensation, muscle control, and coordination. […] The term malignant or high-grade glioma refers to tumors that are classified as: Grade 3 (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic ependymoma) and Grade 4 (glioblastoma). […] Astrocytomas, oligodendrogliomas, and glioblastomas are further classified based on whether they have a genetic change in the isocitrate dehydrogenase (IDH) gene. If there is a mutation, the tumor is designated as IDH mutant, and if there is no mutation, the tumor is designated as IDH wildtype. IDH-wildtype tumors are more aggressive and behave like high-grade glioma.

• #109

  https://consensus.app/questions/malignant-brain-tumor-types/

  Malignant brain tumors are a diverse group of cancers originating within the brain or central nervous system (CNS). These tumors are known for their aggressive nature and poor prognosis. […] Recent advances in molecular biology have significantly improved our understanding of the pathogenesis of gliomas. Key genetic alterations, such as IDH mutations, 1p/19q codeletion, and H3 Lys27Met, are now integrated into the classification and diagnosis of these tumors. […] The tumor microenvironment (TME) plays a crucial role in the progression and treatment response of malignant brain tumors. […] Despite significant progress in understanding the molecular and genetic underpinnings of malignant brain tumors, effective treatments remain limited. […] Malignant brain tumors, particularly gliomas, represent a significant challenge in neuro-oncology due to their aggressive nature and poor prognosis. Advances in molecular pathology and a deeper understanding of the tumor microenvironment offer hope for the development of more effective treatments.

• #110 Brain Tumor: Symptoms, Signs & Causes

  https://my.clevelandclinic.org/health/diseases/6149-brain-cancer-brain-tumor

  Brain tumors can be malignant (cancerous) or benign (noncancerous). […] Brain tumors can be malignant (cancerous) or benign (noncancerous). Some tumors grow quickly, while others are slow growing. […] Approximately 78% of cancerous primary brain tumors are gliomas. These tumors develop in glial cells, which surround and assist nerve cells. […] Medulloblastoma is another type of cancerous brain tumor. These tumors are fast growing and form at the base of your skull. […] Brain tumors whether cancerous or not can cause serious problems. […] Brain tumors can cause problems by: Directly invading and destroying healthy brain tissue. […] Researchers know brain tumors develop when certain genes on the chromosomes of a cell are damaged and no longer function properly, but they aren’t sure why this happens.

• #111 Brain tumor – Wikipedia

  https://en.wikipedia.org/wiki/Brain_tumor

  Secondary, or metastatic, brain tumors are about four times as common as primary brain tumors, with about half of metastases coming from lung cancer. […] The prognosis of brain cancer depends on the type of cancer diagnosed. Medulloblastoma has a good prognosis with chemotherapy, radiotherapy, and surgical resection while glioblastoma has a median survival of only 15 months even with aggressive chemoradiotherapy and surgery.

• #112 Types of Primary Brain Tumors | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/cancer-care/types/brain-tumors-primary/types

  Glioblastoma is the most aggressive type of brain cancer in adults. The tumors start in astrocyte cells, which support your brains nerve cells in various ways. Glioblastomas can metastasize (spread) through brain tissue and can be difficult to remove. In recent years, doctors at MSK and elsewhere have begun to recognize distinct molecular subtypes of glioblastomas, which may in turn enable us to find new and targeted treatment approaches. […] This cancer starts in your lymphatic systems lymphocytes, which are designed to help you fight off disease and infection. Lymphocytes in your brain, eyes, spinal cord, or the three membranes that cover your brain and spinal cord (called the meninges) can become cancerous and start to grow and spread uncontrollably. PCNSL is more common in people with weakened immune systems. Central nervous system lymphoma of the eye is called ocular lymphoma.

• #113 Brain tumors-General

  https://neuropathology-web.org/chapter7/chapter7aTumorsgeneral.html

  The genetic changes that are involved in BT are briefly outlined in the following descriptions of each individual BT. […] BT are initially derived from a single progenitor, but later, the genetic instability that is associated with rapid cell replication causes molecular and chromosomal changes to snowball, generating multiple tumor cell clones. […] An increased incidence of BT, especially meningiomas, has been reported in patients who have received radiation to the head (even low-dose radiation) for a variety of reasons. […] A variety of substances can induce mesenchymal and glial CNS tumors in animals by direct intracerebral inoculation and by oral and parenteral administration. […] The finding of EBV DNA suggests that some of these tumors arise from EBV-infected B-cells.

• #114 Understanding genetic factors behind a pediatric brain tumor and possible treatments

  https://medicalxpress.com/news/2025-05-genetic-factors-pediatric-brain-tumor.html

  Pediatric pilocytic astrocytoma (PA) is a common type of low-grade brain tumor in children, influenced by specific genetic changes. Researchers at Washington University School of Medicine in St. Louis have conducted a study using advanced stem cell techniques to investigate the genetic alterations that cause PA and how they affect tumor growth. Their findings shed light on molecular pathways that could lead to new targeted therapies, offering hope for better treatment options for children with PA. […] PA is mainly driven by two genetic changes: the loss of the Neurofibromatosis type 1 (NF1) gene and a rearrangement of KIAA1549: BRAF, which fuses with the KIAA1549 gene. These anomalies activate the MEK/ERK signaling pathway, which promotes cell growth—a key factor in tumor development. […] The researchers discovered that β-catenin, a protein, is crucial for MEK-dependent cell growth. MEK controls β-catenin activity through two separate mechanisms; IRX2 affects the gene that produces β-catenin, while NPTX1 stabilizes the β-catenin protein, preventing its breakdown.

• #115 Brain tumor – Wikipedia

  https://en.wikipedia.org/wiki/Brain_tumor

  Secondary, or metastatic, brain tumors are about four times as common as primary brain tumors, with about half of metastases coming from lung cancer. […] The prognosis of brain cancer depends on the type of cancer diagnosed. Medulloblastoma has a good prognosis with chemotherapy, radiotherapy, and surgical resection while glioblastoma has a median survival of only 15 months even with aggressive chemoradiotherapy and surgery.

• #116 Brain Tumor Facts

  https://braintumor.org/brain-tumors/about-brain-tumors/brain-tumor-facts/

  35.7% Relative Survival Rate for all patients with a malignant brain tumor […] For patients with malignant brain tumors, the five-year relative survival rate following diagnosis is 35.7% […] For the most common form of primary malignant brain tumors, glioblastoma, the five-year relative survival rate is only 6.9% and median survival is only 8 months. […] Survival rates for adult and pediatric patients with brain tumors have not changed significantly over the past 45 years despite major improvements made in the treatment of other cancers. […] Only a few treatments have ever been approved for the more than 100 types of brain tumors. None of these extend survival more than two years on average, or are considered to be curative. […] Metastatic brain tumors are five times more common than primary brain tumors (those that originate in the brain).

• #117 Neuro-Oncology | OncologyPRO

  https://oncologypro.esmo.org/education-library/esmo-books/essentials-for-clinicians/neuro-oncology/1-epidemiology-pathogenesis-risk-factors-of-brain-tumours

  Brain tumours is the common term to define central nervous system (CNS) neoplasms, or CNS tumours. […] The 2016 World Health Organization classification of CNS tumours is based on histopathological and molecular criteria and includes malignant, benign and borderline tumours. […] Secondary CNS tumours are CNS metastases; they are all malignant. […] Metastatic tumours are the most frequent type of CNS tumour in adults. […] The reported incidence of metastatic CNS tumours is increasing but the exact incidence is unknown. […] In general, the sources of brain metastases (in descending order) are: cancers of the lung, breast, skin (melanoma), kidney and gastrointestinal tract.

• #118 Brain Neoplasms: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/779664-overview

  Most primary brain tumors do not metastasize, but if they do metastasize, intracranial spread generally precedes distant dissemination. […] Metastatic brain tumors from non-CNS primary tumors may be the first sign of malignancy, or they may herald a relapse. Nonetheless, the signs and symptoms of brain metastases simulate those of primary brain tumors. […] Leptomeningeal infiltration may present with dysfunction of multiple cranial nerves.

• #119 Brain Neoplasms: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/779664-overview

  Tumors of the brain produce neurologic manifestations through a number of mechanisms. Small, critically located tumors may damage specific neural pathways traversing the brain. Tumors can invade, infiltrate, or supplant normal parenchymal tissue, disrupting normal function. Because the brain dwells in the limited volume of the cranial vault, growth of intracranial tumors with accompanying edema may cause increased intracranial pressure. Tumors adjacent to the third and fourth ventricles may impede the flow of cerebrospinal fluid, leading to obstructive hydrocephalus. In addition, tumors generate new blood vessels (ie, angiogenesis), disrupting the normal blood-brain barrier and promoting edema. […] The cumulative effects of tumor invasion, edema, and hydrocephalus may elevate the intracranial pressure (ICP) and impair cerebral perfusion. Intracranial compartmental rise in ICP may provoke shifting or herniation of tissue under the falx cerebri, through the tentorium cerebelli, or through the foramen magnum.

• #120 Brain Tumor: Symptoms, Signs & Causes

  https://my.clevelandclinic.org/health/diseases/6149-brain-cancer-brain-tumor

  Brain tumors can be malignant (cancerous) or benign (noncancerous). […] Brain tumors can be malignant (cancerous) or benign (noncancerous). Some tumors grow quickly, while others are slow growing. […] Approximately 78% of cancerous primary brain tumors are gliomas. These tumors develop in glial cells, which surround and assist nerve cells. […] Medulloblastoma is another type of cancerous brain tumor. These tumors are fast growing and form at the base of your skull. […] Brain tumors whether cancerous or not can cause serious problems. […] Brain tumors can cause problems by: Directly invading and destroying healthy brain tissue. […] Researchers know brain tumors develop when certain genes on the chromosomes of a cell are damaged and no longer function properly, but they aren’t sure why this happens.

• #121 Brain Neoplasms: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/779664-overview

  Tumors of the brain produce neurologic manifestations through a number of mechanisms. Small, critically located tumors may damage specific neural pathways traversing the brain. Tumors can invade, infiltrate, or supplant normal parenchymal tissue, disrupting normal function. Because the brain dwells in the limited volume of the cranial vault, growth of intracranial tumors with accompanying edema may cause increased intracranial pressure. Tumors adjacent to the third and fourth ventricles may impede the flow of cerebrospinal fluid, leading to obstructive hydrocephalus. In addition, tumors generate new blood vessels (ie, angiogenesis), disrupting the normal blood-brain barrier and promoting edema. […] The cumulative effects of tumor invasion, edema, and hydrocephalus may elevate the intracranial pressure (ICP) and impair cerebral perfusion. Intracranial compartmental rise in ICP may provoke shifting or herniation of tissue under the falx cerebri, through the tentorium cerebelli, or through the foramen magnum.

• #122 Brain Neoplasms: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/779664-overview

  Tumors of the brain produce neurologic manifestations through a number of mechanisms. Small, critically located tumors may damage specific neural pathways traversing the brain. Tumors can invade, infiltrate, or supplant normal parenchymal tissue, disrupting normal function. Because the brain dwells in the limited volume of the cranial vault, growth of intracranial tumors with accompanying edema may cause increased intracranial pressure. Tumors adjacent to the third and fourth ventricles may impede the flow of cerebrospinal fluid, leading to obstructive hydrocephalus. In addition, tumors generate new blood vessels (ie, angiogenesis), disrupting the normal blood-brain barrier and promoting edema. […] The cumulative effects of tumor invasion, edema, and hydrocephalus may elevate the intracranial pressure (ICP) and impair cerebral perfusion. Intracranial compartmental rise in ICP may provoke shifting or herniation of tissue under the falx cerebri, through the tentorium cerebelli, or through the foramen magnum.

• #123 Brain Tumor: A Comprehensive Guide by Dr. Kamran Aghayev

  https://kamranaghayev.com/brain-tumor/

  A brain tumor is an abnormal growth in the brain, causing compression and loss of important functions. […] A growing tumor has to come at the expense of losing the volume of other components in the cranial cavity. Therefore, the brain tissue, cerebrospinal fluid and blood in the brain circulation have to retract to make extra room for space occupying tumor. This mechanism is called compensation and at this stage the intracranial pressure is not elevated. […] Once compensation mechanisms have been exhausted the intracranial pressure rapidly rises leading to life threatening disruptions of vital brain functions. […] Pain is caused either by elevated intracranial pressure compressing and stretching the dura mater or due to direct invasion of the dura by tumor. […] Gliomas originate and grow inside of the brain.

• #124 Brain Neoplasms: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/779664-overview

  Tumors of the brain produce neurologic manifestations through a number of mechanisms. Small, critically located tumors may damage specific neural pathways traversing the brain. Tumors can invade, infiltrate, or supplant normal parenchymal tissue, disrupting normal function. Because the brain dwells in the limited volume of the cranial vault, growth of intracranial tumors with accompanying edema may cause increased intracranial pressure. Tumors adjacent to the third and fourth ventricles may impede the flow of cerebrospinal fluid, leading to obstructive hydrocephalus. In addition, tumors generate new blood vessels (ie, angiogenesis), disrupting the normal blood-brain barrier and promoting edema. […] The cumulative effects of tumor invasion, edema, and hydrocephalus may elevate the intracranial pressure (ICP) and impair cerebral perfusion. Intracranial compartmental rise in ICP may provoke shifting or herniation of tissue under the falx cerebri, through the tentorium cerebelli, or through the foramen magnum.

• #125 Patient education: High-grade glioma in adults (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-grade-glioma-in-adults-beyond-the-basics

  Gliomas cause symptoms by invading (growing) into and/or creating pressure in nearby normal brain tissue. […] Treatment of a high-grade glioma includes measures to relieve symptoms and eliminate or control the tumor. […] Because there are not curative treatments for most types of high-grade glioma, many people are encouraged to participate in a clinical trial, if possible. […] Radiation therapy uses high-energy x-rays to kill cancer cells and is usually recommended following surgery to kill any remaining tumor cells. […] Bevacizumab (Brand name: Avastin) is an antibody (a type of protein) that targets a protein called vascular endothelial growth factor (VEGF). VEGF causes a growing cancer to develop its own blood supply, which is essential for the tumor to grow and spread. Bevacizumab disrupts the process of new blood vessel formation, thereby depriving the tumor of its supply of nutrients.

• #126 Overview of Intracranial Tumors – Neurologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/neurologic-disorders/intracranial-and-spinal-tumors/overview-of-intracranial-tumors

  A malignant tumor can develop new internal blood vessels, which can bleed or become occluded, resulting in necrosis and neurologic dysfunction that mimics stroke. […] Malignant primary tumors grow rapidly but rarely spread beyond the CNS. Death results from local tumor growth and/or tumor-related hemorrhage and thus can result from benign as well as malignant tumors. […] Deterioration in mental status is the second most common symptom. Manifestations include drowsiness, lethargy, personality changes, disordered conduct, and impaired cognition, particularly with malignant brain tumors. […] Treatment of metastatic tumors includes radiation therapy, which can be delivered as whole-brain or conformal stereotactic radiosurgery.

• #127 Brain Tumor: A Comprehensive Guide by Dr. Kamran Aghayev

  https://kamranaghayev.com/brain-tumor/

  A brain tumor is an abnormal growth in the brain, causing compression and loss of important functions. […] A growing tumor has to come at the expense of losing the volume of other components in the cranial cavity. Therefore, the brain tissue, cerebrospinal fluid and blood in the brain circulation have to retract to make extra room for space occupying tumor. This mechanism is called compensation and at this stage the intracranial pressure is not elevated. […] Once compensation mechanisms have been exhausted the intracranial pressure rapidly rises leading to life threatening disruptions of vital brain functions. […] Pain is caused either by elevated intracranial pressure compressing and stretching the dura mater or due to direct invasion of the dura by tumor. […] Gliomas originate and grow inside of the brain.

• #128 NHS England » Urgent GP direct access to diagnostic services for people with symptoms not meeting the threshold for an urgent suspected cancer referral

  https://www.england.nhs.uk/long-read/urgent-gp-direct-access-to-diagnostic-services-for-people-with-symptoms-not-meeting-the-threshold-for-an-urgent-suspected-cancer-referral/

  Most patients with primary brain tumours have seen their GP before diagnosis, sometimes several times. However, over 50% are diagnosed following emergency presentation. Only 1% of patients with brain tumour are referred via an urgent suspected cancer pathway. GP access to brain MRI is essential to support the earlier and faster diagnosis of brain tumours in primary care. […] Research shows that referral for a suspected brain tumour based on headache alone has a positive predictive value of 0.1%. This means that headache alone is unlikely to indicate a tumour, but if it clearly progresses in frequency and severity and/or is combined with new neurological symptoms, especially cognitive decline or a combination of symptoms, it may be significant. […] GPs should consider whether a brain MRI is warranted for new persistent or progressive headache plus new or progressive cognitive decline/cognitive change, changes in speech word finding difficulty, using the wrong words, semantic verbal fluency test (SVFT) score 17 (inability to name at least 17 different animals in 1 minute), personality change, objectively confirmed visual deficits, particularly visual field loss (can be assessed by a high-street optician), unilateral arm or leg weakness, unilateral sensory change. […] The threshold for brain imaging should be lower in patients with a previous cancer diagnosis, especially lung, breast, melanoma and renal. […] New onset seizures and new onset focal neurological change should continue to be referred via acute pathways.

• #129 Overview of Intracranial Tumors – Neurologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/neurologic-disorders/intracranial-and-spinal-tumors/overview-of-intracranial-tumors

  A malignant tumor can develop new internal blood vessels, which can bleed or become occluded, resulting in necrosis and neurologic dysfunction that mimics stroke. […] Malignant primary tumors grow rapidly but rarely spread beyond the CNS. Death results from local tumor growth and/or tumor-related hemorrhage and thus can result from benign as well as malignant tumors. […] Deterioration in mental status is the second most common symptom. Manifestations include drowsiness, lethargy, personality changes, disordered conduct, and impaired cognition, particularly with malignant brain tumors. […] Treatment of metastatic tumors includes radiation therapy, which can be delivered as whole-brain or conformal stereotactic radiosurgery.

• #130 Glioblastoma – Wikipedia

  https://en.wikipedia.org/wiki/Glioblastoma

  GBMs usually form in the cerebral white matter, grow quickly, and can become very large before producing symptoms. […] Once cancerous, these cells are predisposed to spread along existing paths in the brain, typically along white-matter tracts, blood vessels and the perivascular space. […] Glioblastoma has been associated with the viruses SV40, HHV-6, and cytomegalovirus (CMV). Infection with an oncogenic CMV may even be necessary for the development of glioblastoma. […] Glioblastoma cells with properties similar to progenitor cells (glioblastoma cancer stem cells) have been found in glioblastomas. Their presence, coupled with the glioblastoma’s diffuse nature results in difficulty in removing them completely by surgery, and is therefore believed to be the possible cause behind resistance to conventional treatments, and the high recurrence rate.

• #131 Glioblastoma – Wikipedia

  https://en.wikipedia.org/wiki/Glioblastoma

  GBMs usually form in the cerebral white matter, grow quickly, and can become very large before producing symptoms. […] Once cancerous, these cells are predisposed to spread along existing paths in the brain, typically along white-matter tracts, blood vessels and the perivascular space. […] Glioblastoma has been associated with the viruses SV40, HHV-6, and cytomegalovirus (CMV). Infection with an oncogenic CMV may even be necessary for the development of glioblastoma. […] Glioblastoma cells with properties similar to progenitor cells (glioblastoma cancer stem cells) have been found in glioblastomas. Their presence, coupled with the glioblastoma’s diffuse nature results in difficulty in removing them completely by surgery, and is therefore believed to be the possible cause behind resistance to conventional treatments, and the high recurrence rate.

• #132 Brain Tumor Facts

  https://braintumor.org/brain-tumors/about-brain-tumors/brain-tumor-facts/

  35.7% Relative Survival Rate for all patients with a malignant brain tumor […] For patients with malignant brain tumors, the five-year relative survival rate following diagnosis is 35.7% […] For the most common form of primary malignant brain tumors, glioblastoma, the five-year relative survival rate is only 6.9% and median survival is only 8 months. […] Survival rates for adult and pediatric patients with brain tumors have not changed significantly over the past 45 years despite major improvements made in the treatment of other cancers. […] Only a few treatments have ever been approved for the more than 100 types of brain tumors. None of these extend survival more than two years on average, or are considered to be curative. […] Metastatic brain tumors are five times more common than primary brain tumors (those that originate in the brain).

• #133 Signaling pathways in brain tumors and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01260-z

  Grading using Arabic numerals is recommended, as highlighted by WHO CNS5. […] GBM accounts for 57% of all gliomas while 48% of primary CNS malignancies in HGG, have a median survival time of fewer than 2 years. […] O6 methylguanine DNA methyltransferase (MGMT) is a repair protein that is encoded by the MGMT gene, which can reverse DNA alkylation by depleting itself. […] In patients with MGMT promoter methylation found in 30-50% of isocitrate dehydrogenase (IDH)-wt GBM, gene promoter methylation would repress the expression of this gene. […] Therefore, with MGMT promoter methylation, glioma patients benefit more from treatment with TMZ. […] However, a discordance of MGMT promoter methylation with protein expression was detected in various patient. […] This may be related to the regulation of MGMT protein by Wnt signaling in addition to the regulation of MGMT promoter methylation.

• #134 Glioblastoma: Overview of Disease and Treatment | Oncology Nursing Society

  https://www.ons.org/publications-research/cjon/20/5/supplement-october-2016-glioblastoma-treatment/glioblastoma

  An analysis by Johnson and ONeill (2012) demonstrated a statistically significant improvement in OS since the onset of aggressive multimodality treatment. […] The analysis of this trial also led to the identification of another strong predictor of patient-related outcomes: the methylation of the MGMT gene, located on chromosome 10q26. […] Patients who have methylated (not activated) MGMT exhibit compromised DNA repair. […] Therefore, the expression of methylated MGMT is beneficial for patients undergoing TMZ chemotherapy and RT. […] Despite maximal initial resection and multimodality therapy, about 70% of GBM patients will experience disease progression within one year of diagnosis. […] Re-resection is an option for some patients, and surgical debulking can alleviate mass effect and symptoms, such as seizures, speech, and motor deficits, frequently seen at recurrence.

• #135 Brain Tumor Glossary

  https://braintumor.org/brain-tumors/diagnosis-treatment/diagnosis/brain-tumor-glossary/

  Malignant Brain Tumors contain cancer cells and often do not have clear borders. They are considered to be life-threatening because they grow rapidly and invade surrounding brain tissue. Although malignant brain tumors very rarely spread to other areas of the body, they can spread throughout the brain or to the spine. These tumors can be treated with surgery, chemotherapy and radiation, but they may recur after treatment. […] IDH has three forms, IDH1, IDH2, and IDH3. Mutated forms of IDH1 and IDH2 are often found in gliomas, typically low-grade gliomas and secondary glioblastomas (though IDH1 mutations are occasionally found in primary GBM patients, as well). These mutations, which occur early in the tumor-forming process, change the function of the enzymes, causing them to produce a metabolite called 2-hydroxyglutarate (2HG), instead of a molecule called NADPH. The presence of an IDH mutation in patients tumors is a biomarker for improved prognosis. This means that glioma patients that have an IDH mutation tend to live longer than patients without an IDH mutation (IDH-wide-type). […] Tumorigenesis is the process of transformation of normal cells into tumor cells.

• #136 Signaling pathways in brain tumors and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01260-z

  The production of R-2HG makes IDH mutant cells sensitive to alkylating agents. […] The clinically significant bifunctional alkylating agents procarbazine and CCNU/lomustine induces highly genotoxic DNA interstrand crosslinks, and are a part of the PCV chemotherapeutic regimen successfully utilized in combination with radiotherapy for the treatment of brain tumors with IDH mutation status. […] The vascular endothelial growth factor receptor (VEGFR) signaling pathway has been considered a key factor in GBM tumor survival. […] Bevacizumab inhibits angiogenesis by acting as a humanized monoclonal antibody against the VEGF-A ligand. […] The transforming growth factor beta (TGF-) protein family has complicated functions in diverse regulatory pathways, where TGF-2 is a T cell inhibitor in the GBM tumor microenvironment that is found in approximately 90% of GBM tumor cells. […] The above crucial signaling pathways involved in glioma were demonstrated in Fig. 2.

• #137

  https://consensus.app/questions/malignant-brain-tumor-types/

  Malignant brain tumors are a diverse group of cancers originating within the brain or central nervous system (CNS). These tumors are known for their aggressive nature and poor prognosis. […] Recent advances in molecular biology have significantly improved our understanding of the pathogenesis of gliomas. Key genetic alterations, such as IDH mutations, 1p/19q codeletion, and H3 Lys27Met, are now integrated into the classification and diagnosis of these tumors. […] The tumor microenvironment (TME) plays a crucial role in the progression and treatment response of malignant brain tumors. […] Despite significant progress in understanding the molecular and genetic underpinnings of malignant brain tumors, effective treatments remain limited. […] Malignant brain tumors, particularly gliomas, represent a significant challenge in neuro-oncology due to their aggressive nature and poor prognosis. Advances in molecular pathology and a deeper understanding of the tumor microenvironment offer hope for the development of more effective treatments.

• #138 Glioblastoma Multiforme Study – NCI

  https://www.cancer.gov/ccg/research/genome-sequencing/tcga/studied-cancers/glioblastoma-multiforme-study

  Glioblastoma Multiforme (GBM) is a fast-growing type of malignant brain tumor that is the most common brain tumor in adults. […] Patients with GBM have a poor prognosis and usually survive less than 15 months following diagnosis. […] Selective pressure to lose mismatch repair function may cause some tumors to become resistant to therapy after treatment with a standard chemotherapy called temozolomide. This finding could be used to develop new strategies that will not activate this drug resistance mechanism. […] Alterations of the EGFR gene as well as a region on a chromosome containing MDM2 and CDK4 genes may be important to the development of GBM. […] GBM mutations are enriched for chromatin modification genes.

• #139 Glioblastoma Multiforme – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558954/

  Glioblastoma multiforme (GBM) is the most malignant and pervasive subtype of glioma and is the most common primary brain tumor in adults. […] The only well-established causative factor is exposure to high doses of ionizing radiation. […] GBM shows features of immune escape and high tumor heterogeneity. Moreover, the relative immune privileged milieu owing to the lack of antigen-presenting cells (APCs) and lymphatics within the CNS further contributes to the poor prognosis among cohorts with GBM. […] Malignant cells have abnormal proliferation, growth, and angiogenesis due to mutations. […] GBM is found to have many genetic and epigenetic mutations. The mutations are essential to identify and classify to understand the tumor behavior and treatment resistance throughout the clinical course.

• #140 Frontiers | Iron Transporters and Ferroptosis in Malignant Brain Tumors

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.861834/full

  Malignant brain tumors are commonly intratumoral heterogenic, which likely explains their poor clinical prognosis of malignant brain tumors poor and easy to relapse. Despite current multimodality treatment efforts, combining in surgical resection when feasible, with radiotherapy, chemotherapy and symptomatic treatment, the median survival remains short. […] Ferroptosis occurs when iron overload induces lipid peroxidation. Recent studies showed that ferroptosis is involved in the death of pathological cells in malignant brain tumors, which may have a therapeutic potential towards malignant brain tumors. […] Starting from the iron transport in the body under physiological conditions, we further summarize the specific mechanism of iron metabolism disorder and ferroptosis in the pathological condition of malignant brain tumors, in particular, the crucial role of transporters.

• #141 Why Do Brain Tumors Often Return After Treatment? MSK Researchers Say Stem Cells May Be Key | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/news/why-do-brain-tumors-often-return-after-treatment-msk-researchers-say-stem-cells-may-be-key

  Glioblastoma brain tumors are one of the most deadly forms of cancer, with a five-year survival rate of less than 10% for patients 45 and older. Even when the tumors look as if they have been fully removed, they almost always come back. […] The standard therapy for glioblastoma targets actively dividing cells, says BTC Director Luis Parada, the papers senior author, who came to MSK in 2015 to develop a comprehensive program for fighting brain tumors. But here, we demonstrate the existence of a small percentage of dormant, stem-like cells that evade these therapies and reinitiate tumor development. […] Traditional chemotherapy and radiation therapy go after cells that are quickly growing and dividing a characteristic of most cancer cells. But in glioblastoma tumors, some cells are quiescent. That means they are essentially in a dormant, resting state hiding out from treatments aimed at cell division.

• #142 Why Do Brain Tumors Often Return After Treatment? MSK Researchers Say Stem Cells May Be Key | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/news/why-do-brain-tumors-often-return-after-treatment-msk-researchers-say-stem-cells-may-be-key

  We found that quiescent cells very gradually give rise to dividing cells, which allow tumors to grow again, explains Dr. Parada, who is a member of the Cancer Biology and Genetics Program in the Sloan Kettering Institute. […] This research shows why therapies that focus only on cell division are insufficient for treating glioblastoma and reinforce the need for developing new strategies that target quiescent cells, Dr. Parada says. The discovery of activated cancer stem cells in mouse models provides us with unprecedented opportunity to investigate their unique features and self-renewal mechanisms, which will help in our ongoing efforts to find a cure for glioblastoma.

• #143 Glioblastoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/283252-overview

  Glioblastomas are among the most malignant of human neoplasms and have one of the worst survival rates of any brain tumor. […] Recurrence, or regrowth of tumor after a period of complete remission or stable disease, is nearly universal in glioblastoma and typically occurs within 7 months of initial treatment. […] While the past few decades have seen marginal improvements in overall survival, new approaches to the management of glioblastoma are clearly needed.

• #144 Glioblastoma: Overview of Disease and Treatment | Oncology Nursing Society

  https://www.ons.org/publications-research/cjon/20/5/supplement-october-2016-glioblastoma-treatment/glioblastoma

  An analysis by Johnson and ONeill (2012) demonstrated a statistically significant improvement in OS since the onset of aggressive multimodality treatment. […] The analysis of this trial also led to the identification of another strong predictor of patient-related outcomes: the methylation of the MGMT gene, located on chromosome 10q26. […] Patients who have methylated (not activated) MGMT exhibit compromised DNA repair. […] Therefore, the expression of methylated MGMT is beneficial for patients undergoing TMZ chemotherapy and RT. […] Despite maximal initial resection and multimodality therapy, about 70% of GBM patients will experience disease progression within one year of diagnosis. […] Re-resection is an option for some patients, and surgical debulking can alleviate mass effect and symptoms, such as seizures, speech, and motor deficits, frequently seen at recurrence.

• #145 Glioblastoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/283252-overview

  Glioblastomas are among the most malignant of human neoplasms and have one of the worst survival rates of any brain tumor. […] Recurrence, or regrowth of tumor after a period of complete remission or stable disease, is nearly universal in glioblastoma and typically occurs within 7 months of initial treatment. […] While the past few decades have seen marginal improvements in overall survival, new approaches to the management of glioblastoma are clearly needed.

• #146 Brain Tumor Facts

  https://braintumor.org/brain-tumors/about-brain-tumors/brain-tumor-facts/

  35.7% Relative Survival Rate for all patients with a malignant brain tumor […] For patients with malignant brain tumors, the five-year relative survival rate following diagnosis is 35.7% […] For the most common form of primary malignant brain tumors, glioblastoma, the five-year relative survival rate is only 6.9% and median survival is only 8 months. […] Survival rates for adult and pediatric patients with brain tumors have not changed significantly over the past 45 years despite major improvements made in the treatment of other cancers. […] Only a few treatments have ever been approved for the more than 100 types of brain tumors. None of these extend survival more than two years on average, or are considered to be curative. […] Metastatic brain tumors are five times more common than primary brain tumors (those that originate in the brain).

• #147 Signaling pathways in brain tumors and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01260-z

  Brain tumors, although rare, contribute to distinct mortality and morbidity at all ages. […] Nonetheless, the reduced response rates and unavoidable drug resistance of currently available treatment approaches have become a barrier to further improvement in brain tumor (glioma, meningioma, CNS germ cell tumors, and CNS lymphoma) treatment. […] Importantly, a better understanding of targeting signaling pathways that influences malignant behavior of brain tumor cells might open the way for the development of novel targeted therapies. […] Thus, there is an urgent need for a more comprehensive understanding of the pathogenesis of these brain tumors, which might result in greater progress in therapeutic approaches. […] The major signaling pathways underlying these brain tumors pathogenesis and current progress in therapies, including clinical trials, targeted therapies, immunotherapies, and system therapies, have been systemically reviewed and discussed.

• #148 Glioblastoma Multiforme – AANS

  https://www.aans.org/patients/conditions-treatments/glioblastoma-multiforme/

  Next generation sequencing aids molecular analysis and in profiling brain tumors to improve diagnostic accuracy, therapeutic target identification and predict prognosis. […] The mainstay of treatment for GBMs is surgery, followed by radiation and chemotherapy. […] However, GBMs are surrounded by a zone of migrating, infiltrating tumor cells that invade surrounding tissues, making it impossible to ever remove the tumor entirely. […] The use of radiation therapy provides most patients with improved outcomes and longer survival rates compared to surgery alone or the best supportive care. […] Chemotherapy with the drug temozolomide is the current standard of treatment for GBM.

• #149 Glioblastoma Multiforme – AANS

  https://www.aans.org/patients/conditions-treatments/glioblastoma-multiforme/

  Next generation sequencing aids molecular analysis and in profiling brain tumors to improve diagnostic accuracy, therapeutic target identification and predict prognosis. […] The mainstay of treatment for GBMs is surgery, followed by radiation and chemotherapy. […] However, GBMs are surrounded by a zone of migrating, infiltrating tumor cells that invade surrounding tissues, making it impossible to ever remove the tumor entirely. […] The use of radiation therapy provides most patients with improved outcomes and longer survival rates compared to surgery alone or the best supportive care. […] Chemotherapy with the drug temozolomide is the current standard of treatment for GBM.

• #150 Glioblastoma: Overview of Disease and Treatment | Oncology Nursing Society

  https://www.ons.org/publications-research/cjon/20/5/supplement-october-2016-glioblastoma-treatment/glioblastoma

  Additional radiation may be possible for some patients, but tolerance of healthy brain tissue to radiation is limited because of the increased risk of radiation necrosis. […] Upon recurrence of GBM, chemotherapy and corticosteroids may be used to palliate symptoms and improve quality of life, but objective response rates are dismal, and time to progression for standard cytotoxic agents is only three to six months. […] The lack of significant side effects from the device, primarily scalp irritation from the arrays (electrodes), makes TTFields an attractive treatment option.

• #151 Glioblastoma Multiforme – AANS

  https://www.aans.org/patients/conditions-treatments/glioblastoma-multiforme/

  Next generation sequencing aids molecular analysis and in profiling brain tumors to improve diagnostic accuracy, therapeutic target identification and predict prognosis. […] The mainstay of treatment for GBMs is surgery, followed by radiation and chemotherapy. […] However, GBMs are surrounded by a zone of migrating, infiltrating tumor cells that invade surrounding tissues, making it impossible to ever remove the tumor entirely. […] The use of radiation therapy provides most patients with improved outcomes and longer survival rates compared to surgery alone or the best supportive care. […] Chemotherapy with the drug temozolomide is the current standard of treatment for GBM.

• #152 Signaling pathways in brain tumors and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01260-z

  The production of R-2HG makes IDH mutant cells sensitive to alkylating agents. […] The clinically significant bifunctional alkylating agents procarbazine and CCNU/lomustine induces highly genotoxic DNA interstrand crosslinks, and are a part of the PCV chemotherapeutic regimen successfully utilized in combination with radiotherapy for the treatment of brain tumors with IDH mutation status. […] The vascular endothelial growth factor receptor (VEGFR) signaling pathway has been considered a key factor in GBM tumor survival. […] Bevacizumab inhibits angiogenesis by acting as a humanized monoclonal antibody against the VEGF-A ligand. […] The transforming growth factor beta (TGF-) protein family has complicated functions in diverse regulatory pathways, where TGF-2 is a T cell inhibitor in the GBM tumor microenvironment that is found in approximately 90% of GBM tumor cells. […] The above crucial signaling pathways involved in glioma were demonstrated in Fig. 2.

• #153 Signaling pathways in brain tumors and therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-022-01260-z

  The production of R-2HG makes IDH mutant cells sensitive to alkylating agents. […] The clinically significant bifunctional alkylating agents procarbazine and CCNU/lomustine induces highly genotoxic DNA interstrand crosslinks, and are a part of the PCV chemotherapeutic regimen successfully utilized in combination with radiotherapy for the treatment of brain tumors with IDH mutation status. […] The vascular endothelial growth factor receptor (VEGFR) signaling pathway has been considered a key factor in GBM tumor survival. […] Bevacizumab inhibits angiogenesis by acting as a humanized monoclonal antibody against the VEGF-A ligand. […] The transforming growth factor beta (TGF-) protein family has complicated functions in diverse regulatory pathways, where TGF-2 is a T cell inhibitor in the GBM tumor microenvironment that is found in approximately 90% of GBM tumor cells. […] The above crucial signaling pathways involved in glioma were demonstrated in Fig. 2.

• #154 New therapy for glioma receives FDA approval | Duke Department of Neurosurgery

  https://neurosurgery.duke.edu/news/new-therapy-glioma-receives-fda-approval

  The discovery of the mutant IDH gene is one of the most important discoveries in neuro-oncology. The IDH mutation has been incorporated by the World Health Organization into the rapid and accurate diagnosis and classification of astrocytic, oligodendroglial, and glioblastoma multiforme brain tumors. Never before has there been a single gene mutation that contributed so greatly to classification. Most importantly, it was immediately recognized that the IDH mutation could be targeted with drugs to treat the group of patients that had malignant brain tumors that expressed the IDH mutation. […] Mutations in the IDH1 or IDH2 genes result in elevated levels of the oncometabolite D-2HG, disrupting normal cellular functions and contributing to tumorigenesis. Vorasidenib selectively binds to the mutated IDH1 and IDH2 enzymes, inhibiting their activity and thereby reducing the production of D-2HG. This inhibition helps to restore normal cellular processes, reduce tumor cell proliferation, and promote the differentiation of cancer cells.

• #155 Brain Tumor & Glioblastoma Multiforme (GBM) – Everfront Biotech

  https://www.efbiotech.com/wordpress/?page_id=5824

  Glioblastoma Multiforme (GBM) can grow up to 16 times its size within one month and is a rapidly worsening primary brain tumor. The recurrence rate after surgery is also very high, often requiring patients to repeatedly undergo hospital treatments. Patients diagnosed with stage IV GBM have an average survival time of only 12 to 18 months. Malignant brain tumors spread rapidly and are challenging to eradicate. […] Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor that can grow up to 16 times its original size within a month. It has a high rate of recurrence after surgical resection, and there are currently no effective treatment options available. […] The core concept of immunotherapy is to harness the body’s immune system to attack and destroy brain tumor cells. […] Gliadel Wafer is an implantable treatment for GBM (Glioblastoma Multiforme). It is a biodegradable polymer-based circular wafer containing the chemotherapy drug Carmustine.

• #156 New mRNA cancer vaccine triggers fierce immune response to fight malignant brain tumor – UF Health

  https://ufhealth.org/news/2024/uf-developed-mrna-vaccine-triggers-fierce-immune-response-to-fight-malignant-brain-tumor

  In a first-ever human clinical trial of four adult patients, an mRNA cancer vaccine developed at UF quickly reprogrammed the immune system to attack glioblastoma, the most aggressive and lethal brain tumor. […] The breakthrough now will be tested in a Phase 1 pediatric clinical trial for brain cancer. […] The new publication is the culmination of promising translational results over seven years of studies, starting in preclinical mouse models and then in a clinical trial of 10 pet dogs that had spontaneously developed terminal brain cancer and had no other treatment options. […] After treating pet dogs that had spontaneously developed brain cancer with personalized mRNA vaccines, Sayour’s team advanced the research to a small Food and Drug Administration-approved clinical trial designed to ensure safety and test feasibility before expanding to a larger trial.

• #157 Glioblastoma: Overview of Disease and Treatment | Oncology Nursing Society

  https://www.ons.org/publications-research/cjon/20/5/supplement-october-2016-glioblastoma-treatment/glioblastoma

  Additional radiation may be possible for some patients, but tolerance of healthy brain tissue to radiation is limited because of the increased risk of radiation necrosis. […] Upon recurrence of GBM, chemotherapy and corticosteroids may be used to palliate symptoms and improve quality of life, but objective response rates are dismal, and time to progression for standard cytotoxic agents is only three to six months. […] The lack of significant side effects from the device, primarily scalp irritation from the arrays (electrodes), makes TTFields an attractive treatment option.

• #158 New therapy for glioma receives FDA approval | Duke Department of Neurosurgery

  https://neurosurgery.duke.edu/news/new-therapy-glioma-receives-fda-approval

  The discovery of the mutant IDH gene is one of the most important discoveries in neuro-oncology. The IDH mutation has been incorporated by the World Health Organization into the rapid and accurate diagnosis and classification of astrocytic, oligodendroglial, and glioblastoma multiforme brain tumors. Never before has there been a single gene mutation that contributed so greatly to classification. Most importantly, it was immediately recognized that the IDH mutation could be targeted with drugs to treat the group of patients that had malignant brain tumors that expressed the IDH mutation. […] Mutations in the IDH1 or IDH2 genes result in elevated levels of the oncometabolite D-2HG, disrupting normal cellular functions and contributing to tumorigenesis. Vorasidenib selectively binds to the mutated IDH1 and IDH2 enzymes, inhibiting their activity and thereby reducing the production of D-2HG. This inhibition helps to restore normal cellular processes, reduce tumor cell proliferation, and promote the differentiation of cancer cells.

• #159 New therapy for glioma receives FDA approval | Duke Department of Neurosurgery

  https://neurosurgery.duke.edu/news/new-therapy-glioma-receives-fda-approval

  The development and approval of vorasidenib represent a significant milestone in the field of oncology, particularly in the treatment of brain cancers. It validates the approach of targeting specific genetic mutations with precision therapies and reinforces the importance of personalized medicine in oncology. […] There are indeed plans to explore the potential of vorasidenib beyond its current indications. Researchers are investigating its use in combination with other therapies, such as immune checkpoint inhibitors, to enhance therapeutic efficacy. Additionally, studies are being planned or are already under way to assess the effectiveness of vorasidenib in treating other types of brain cancers, solid tumors and leukemia with IDH mutations. […] The INDIGO clinical trial was a phase 3 trial of vorasidenib, an oral inhibitor of mutant IDH1/2 that can readily cross the blood-brain barrier, versus placebo in patients with mutant IDH1/2 glioma. Treatment with vorasidenib significantly improved progression-free survival (27.7 months vorasidenib vs. 11.1 for placebo).

• #160 New therapy for glioma receives FDA approval | Duke Department of Neurosurgery

  https://neurosurgery.duke.edu/news/new-therapy-glioma-receives-fda-approval

  The development and approval of vorasidenib represent a significant milestone in the field of oncology, particularly in the treatment of brain cancers. It validates the approach of targeting specific genetic mutations with precision therapies and reinforces the importance of personalized medicine in oncology. […] There are indeed plans to explore the potential of vorasidenib beyond its current indications. Researchers are investigating its use in combination with other therapies, such as immune checkpoint inhibitors, to enhance therapeutic efficacy. Additionally, studies are being planned or are already under way to assess the effectiveness of vorasidenib in treating other types of brain cancers, solid tumors and leukemia with IDH mutations. […] The INDIGO clinical trial was a phase 3 trial of vorasidenib, an oral inhibitor of mutant IDH1/2 that can readily cross the blood-brain barrier, versus placebo in patients with mutant IDH1/2 glioma. Treatment with vorasidenib significantly improved progression-free survival (27.7 months vorasidenib vs. 11.1 for placebo).

• #161 Frontiers | Iron Transporters and Ferroptosis in Malignant Brain Tumors

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.861834/full

  Ferroptosis is a form of iron-dependent regulatory cell death distinguished from necrosis, apoptosis and autophagy, which can be triggered by the small-molecule compound erastin and RSL3. Iron and polyunsaturated fatty acids (PUFAs) act as raw materials for lipid peroxidation to promote the occurrence of ferroptosis. […] Ferroptosis plays a key role in the development of malignant brain tumors. As an important part of ferroptosis, relevant transporters can regulate amino acid metabolism and iron metabolism and are essential for the maintenance of iron homeostasis. Disorders of iron homeostasis in the brain will increase the risk of tumors, which may be one of the factors leading to the increased incidence of brain tumors. […] Inducing ferroptosis of tumor cells is a newly discovered strategy for the treatment of malignant brain tumors, but many problems remain to be solved, including elucidating the mechanism of ferroptosis in different malignant brain tumors, discovering new therapeutic targets for inducing ferroptosis of tumor cells, and increasing the tumor cell targeting of ferroptosis inducers.

• #162 Frontiers | Iron Transporters and Ferroptosis in Malignant Brain Tumors

  https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.861834/full

  Ferroptosis is a form of iron-dependent regulatory cell death distinguished from necrosis, apoptosis and autophagy, which can be triggered by the small-molecule compound erastin and RSL3. Iron and polyunsaturated fatty acids (PUFAs) act as raw materials for lipid peroxidation to promote the occurrence of ferroptosis. […] Ferroptosis plays a key role in the development of malignant brain tumors. As an important part of ferroptosis, relevant transporters can regulate amino acid metabolism and iron metabolism and are essential for the maintenance of iron homeostasis. Disorders of iron homeostasis in the brain will increase the risk of tumors, which may be one of the factors leading to the increased incidence of brain tumors. […] Inducing ferroptosis of tumor cells is a newly discovered strategy for the treatment of malignant brain tumors, but many problems remain to be solved, including elucidating the mechanism of ferroptosis in different malignant brain tumors, discovering new therapeutic targets for inducing ferroptosis of tumor cells, and increasing the tumor cell targeting of ferroptosis inducers.

• #163 New therapy for glioma receives FDA approval | Duke Department of Neurosurgery

  https://neurosurgery.duke.edu/news/new-therapy-glioma-receives-fda-approval

  The development and approval of vorasidenib represent a significant milestone in the field of oncology, particularly in the treatment of brain cancers. It validates the approach of targeting specific genetic mutations with precision therapies and reinforces the importance of personalized medicine in oncology. […] There are indeed plans to explore the potential of vorasidenib beyond its current indications. Researchers are investigating its use in combination with other therapies, such as immune checkpoint inhibitors, to enhance therapeutic efficacy. Additionally, studies are being planned or are already under way to assess the effectiveness of vorasidenib in treating other types of brain cancers, solid tumors and leukemia with IDH mutations. […] The INDIGO clinical trial was a phase 3 trial of vorasidenib, an oral inhibitor of mutant IDH1/2 that can readily cross the blood-brain barrier, versus placebo in patients with mutant IDH1/2 glioma. Treatment with vorasidenib significantly improved progression-free survival (27.7 months vorasidenib vs. 11.1 for placebo).

• #164 Patient education: High-grade glioma in adults (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/high-grade-glioma-in-adults-beyond-the-basics

  Gliomas cause symptoms by invading (growing) into and/or creating pressure in nearby normal brain tissue. […] Treatment of a high-grade glioma includes measures to relieve symptoms and eliminate or control the tumor. […] Because there are not curative treatments for most types of high-grade glioma, many people are encouraged to participate in a clinical trial, if possible. […] Radiation therapy uses high-energy x-rays to kill cancer cells and is usually recommended following surgery to kill any remaining tumor cells. […] Bevacizumab (Brand name: Avastin) is an antibody (a type of protein) that targets a protein called vascular endothelial growth factor (VEGF). VEGF causes a growing cancer to develop its own blood supply, which is essential for the tumor to grow and spread. Bevacizumab disrupts the process of new blood vessel formation, thereby depriving the tumor of its supply of nutrients.

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