Materiały źródłowe

• #1 Epigenomics and immunotherapeutic advances in pediatric brain tumors | npj Precision Oncology

  https://www.nature.com/articles/s41698-021-00173-4

  Brain tumors are the leading cause of childhood cancer-related deaths. […] Recent research findings from molecular genetic analyses have revealed molecular and genetic changes in pediatric tumors that are necessary for appropriate classification to avoid misdiagnosis, the development of treatment modalities, and the clinical management of tumors. […] As many of the molecular-based therapies developed from clinical trials on adults are not always effective against pediatric brain tumors, recent advances have improved our understanding of the molecular profiles of pediatric brain tumors and have led to novel epigenetic and immunotherapeutic treatment approaches currently being evaluated in clinical trials. […] The comparison of pediatric and adult brain tumors highlights the need for treatments designed specifically for pediatric brain tumors.

• #2 Childhood brain tumors: current management, biological insights, and future directions in: Journal of Neurosurgery: Pediatrics Volume 23 Issue 3 (2019) Journals

  https://thejns.org/pediatrics/view/journals/j-neurosurg-pediatr/23/3/article-p261.xml

  Brain tumors are the most common solid tumors in children, and, unfortunately, many subtypes continue to have a suboptimal long-term outcome. […] During the last several years, however, remarkable advances in our understanding of the molecular underpinnings of these tumors have occurred as a result of high-resolution genomic, epigenetic, and transcriptomic profiling, which have provided insights for improved tumor categorization and molecularly directed therapies. […] The situation is even more complex for ependymoma, for which at least nine subsets of tumors have been described. […] Conversely, the majority of pilocytic astrocytomas appear to result from genetic changes that alter a single, therapeutically targetable molecular pathway. […] The feasibility of these goals has been dramatically augmented by the revolution in molecular biology during the last 5-10 years, which has yielded progressively more detailed insights into the genetic basis for virtually every type of childhood brain tumor.

• #3 Pediatric brain tumors – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/pediatric-brain-tumor/symptoms-causes/syc-20361694

  Pediatric brain tumors start when cells in the brain develop changes in their DNA. A cell’s DNA holds the instructions that tell a cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In tumor cells, the DNA changes give different instructions. The changes tell the tumor cells to make many more cells quickly. Tumor cells can keep living when healthy cells would die. This causes too many cells. […] Some tumor cells develop other DNA changes that turn them into cancer cells. Cancer cells can invade and destroy healthy tissue. Sometimes cancer cells can break away and spread beyond the brain. If brain cancer spreads, it tends to go to the fluid that surrounds the brain and spinal cord. This fluid is called cerebrospinal fluid.

• #4 Brain tumor – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/brain-tumor/symptoms-causes/syc-20350084

  Brain tumors happen when cells in or near the brain get changes in their DNA. A cell’s DNA holds the instructions that tell the cell what to do. The changes tell the cells to grow quickly and continue living when healthy cells would die as part of their natural life cycle. This makes a lot of extra cells in the brain. The cells can form a growth called a tumor. […] It’s not clear what causes the DNA changes that lead to brain tumors. For many people with brain tumors, the cause is never known. Sometimes parents pass DNA changes to their children. The changes can increase the risk of having a brain tumor. These hereditary brain tumors are rare. If you have a family history of brain tumors, talk about it with your health care provider. You might consider meeting with a health care provider trained in genetics to understand whether your family history increases your risk of having a brain tumor.

• #5 Brain Tumors in Children – Stanford Medicine Children’s Health

  https://deprod.stanfordchildrens.org/en/topic/default?id=brain-tumors-in-children-90-P02745

  The majority of brain tumors have abnormalities of genes involved in cell cycle control, causing uncontrolled cell growth. These abnormalities are caused by alterations directly in the genes, or by chromosome rearrangements that change the function of a gene. […] Patients with certain genetic conditions (neurofibromatosis, von Hippel-Lindau disease, Li-Fraumeni syndrome, and retinoblastoma) also have an increased risk for developing tumors of the central nervous system. […] Some chemicals may change the structure of a gene that protects the body from diseases and cancer. Research has been investigating parents of children with brain tumors and their past exposure to certain chemicals, including pesticides and petroleum products. […] Children who have received radiation therapy to the head as part of prior treatment for other malignancies are also at an increased risk for new brain tumors.

• #6

  https://link.springer.com/article/10.1007/s11060-004-2750-7

  In the last decade, the molecular biology revolution has advanced considerably. […] We now know that many pediatric brain tumors arise from disturbances in developmentally regulated signaling pathways. […] The medulloblastoma, a tumor in which the developmental Hedgehog and WNT pathways have gone awry, is a prime example of this. […] Many laboratories are now using cDNA microarrays to study the expression level of thousands of genes that may be aberrantly expressed in brain tumors when compared to normal control cells. […] In the next decade, the use of several new molecular techniques to establish brain tumor diagnoses will likely become standard tools in the diagnostics and treatment stratification of children with central nervous system tumors.

• #7

  https://link.springer.com/article/10.1007/s11060-004-2750-7

  In the last decade, the molecular biology revolution has advanced considerably. […] We now know that many pediatric brain tumors arise from disturbances in developmentally regulated signaling pathways. […] The medulloblastoma, a tumor in which the developmental Hedgehog and WNT pathways have gone awry, is a prime example of this. […] Many laboratories are now using cDNA microarrays to study the expression level of thousands of genes that may be aberrantly expressed in brain tumors when compared to normal control cells. […] In the next decade, the use of several new molecular techniques to establish brain tumor diagnoses will likely become standard tools in the diagnostics and treatment stratification of children with central nervous system tumors.

• #8 Molecular Insights into Pediatric Brain Tumors Have the Potential to Transform Therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4234174/

  These advances have been made possible by technologies capable of cataloging the sequence, copy number and expression of all genes. […] These studies have unmasked a common theme in pediatric brain tumors in which molecular discrete subtypes of each tumor likely arise from topographically discrete neural progenitor cells that are selectively susceptible to specific transforming mutations. […] The term medulloblastoma was originally used to describe all small round blue cell tumors of the cerebellum. […] The discovery of hSNF5/INI1 mutations in atypical teratoid/rhabdoid tumors (ATRT), provided the first firm evidence that not all tumors treated as medulloblastoma were the same disease. […] Studies conducted over the last ten years have identified distinct subtypes of medulloblastoma.

• #9 Epigenomics and immunotherapeutic advances in pediatric brain tumors | npj Precision Oncology

  https://www.nature.com/articles/s41698-021-00173-4

  Epigenetic changes are essential to malignant transformation, as tumor tissues exhibit abnormal patterns of methylation compared to healthy tissues. […] Profiling each tumor for epigenetic changes (in addition to gene modifications) will improve stratification in clinical trials and predictions of responses to therapy. […] Tumor cells also use epigenetic mechanisms to escape chemotherapy and host immune surveillance, so improving our understanding of these mechanisms will improve treatment outcomes. […] The association between epigenetic changes and cancer development has become key to understanding cancer development and to developing novel cancer treatments. […] The use of DNA methylation signatures as part of a combined histology and molecular tumor classification for pediatric brain tumors was first demonstrated by Capper et al. on the basis that each brain tumor subtype has discrete genetic and epigenetic profiles. […] Thus, for pediatric CNS tumors, epigenetic modifications can also serve as therapeutic drug targets. […] Epigenetic profiles of pediatric brain tumors can be more informative than their mutational profiles.

• #10 Epigenetic mechanisms regulating neural development and pediatric brain tumor formation in: Journal of Neurosurgery: Pediatrics Volume 8 Issue 2 (2011) Journals

  https://thejns.org/pediatrics/view/journals/j-neurosurg-pediatr/8/2/article-p119.xml

  Pediatric brain tumors are the leading cause of cancer-related death in children, and among them, embryonal tumors represent the largest group with an associated poor prognosis and long-term morbidity for survivors. […] The field of cancer epigenetics has emerged recently as an important area of investigation and causation of a variety of neoplasms, and is defined as alterations in gene expression without changes in DNA sequence. […] The best studied epigenetic modifications are DNA methylation, histone modifications, and RNA-based mechanisms. […] These modifications play an important role in normal development and differentiation but their dysregulation can lead to altered gene function and cancer. […] In this review the authors describe the mechanisms of normal epigenetic regulation, how they interplay in neuroembryogenesis, and how these can cause brain tumors in children when dysregulated. […] The potential use of epigenetic markers to design more effective treatment strategies for children with malignant brain tumors is also discussed.

• #11 Epigenomics and immunotherapeutic advances in pediatric brain tumors | npj Precision Oncology

  https://www.nature.com/articles/s41698-021-00173-4

  Epigenetic changes are essential to malignant transformation, as tumor tissues exhibit abnormal patterns of methylation compared to healthy tissues. […] Profiling each tumor for epigenetic changes (in addition to gene modifications) will improve stratification in clinical trials and predictions of responses to therapy. […] Tumor cells also use epigenetic mechanisms to escape chemotherapy and host immune surveillance, so improving our understanding of these mechanisms will improve treatment outcomes. […] The association between epigenetic changes and cancer development has become key to understanding cancer development and to developing novel cancer treatments. […] The use of DNA methylation signatures as part of a combined histology and molecular tumor classification for pediatric brain tumors was first demonstrated by Capper et al. on the basis that each brain tumor subtype has discrete genetic and epigenetic profiles. […] Thus, for pediatric CNS tumors, epigenetic modifications can also serve as therapeutic drug targets. […] Epigenetic profiles of pediatric brain tumors can be more informative than their mutational profiles.

• #12 Pediatric CNS Tumors – Free Sketchy Medical Lesson

  https://www.sketchy.com/medical-lessons/pediatric-cns-tumors

  In the pediatric population, CNS tumors primarily manifest infratentorially, a in contrast to adult CNS tumors which frequently present supratentorially. […] Risk factors include genetic syndromes like tuberous sclerosis and neurofibromatosis 1, as well as exposure to ionizing radiation. […] Pilocytic astrocytomas are the most common pediatric CNS tumor and are named for their hairlike projections observed under microscopy. These benign, grade 1 tumors frequently contain activating mutations in the BRAF gene, leading to abnormal cell growth. […] Medulloblastomas are the most common malignant CNS tumors in children. They originate from cells that are partially differentiated in the neuronal direction, staining positive for synaptophysin and neuron-specific enolase. […] Ependymomas are CNS tumors that arise from the ependymal cells lining the ventricular system. They most commonly grow from the roof of the 4th ventricle, which can cause intracranial hypertension due to obstructive hydrocephalus.

• #13 Epigenomics and immunotherapeutic advances in pediatric brain tumors | npj Precision Oncology

  https://www.nature.com/articles/s41698-021-00173-4

  Molecular profiling has revealed significant differences between adult and pediatric brain tumors, despite having similar histology. […] The classification of pHGGs is based on molecular subgroups and significant clinical correlations (i.e., age, anatomical location, and prognosis). […] Overall, histone mutations represent slightly more than half of all childhood pHGG cases. […] The largest pHGG dataset to date was used in a retrospective study that revealed ten subgroups based on specific genes and processes and showed that histone mutations cosegregate with distinct modifications and downstream pathways. […] Epigenetic modifications are reversible structural alterations of the nucleic acid and histone proteins that constitute the nucleosome. […] The identification of genes that control epigenetic changes has produced novel targets for cancer treatments, particularly treatments for CNS tumors.

• #14 Brain tumor – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/brain-tumor/symptoms-causes/syc-20350084

  When brain tumors happen in children, they’re likely to be primary brain tumors. In adults, brain tumors are more likely to be cancer that started somewhere else and spread to the brain. […] Secondary brain tumors happen when cancer starts somewhere else and spreads to the brain. When cancer spreads, it’s called metastatic cancer. […] It’s not clear why some cancers spread to the brain and others are more likely to spread to other places. […] In adults, secondary brain tumors are far more common than are primary brain tumors.

• #15 Pediatric Brain Tumors

  https://braintumor.org/brain-tumors/about-brain-tumors/pediatric-brain-tumors/

  There can be differences in the genetic and molecular characteristics of pediatric and adult brain tumors. Certain genetic mutations and markers may be more common in pediatric cases, influencing treatment options and responses. […] Treatment strategies for pediatric and adult brain tumors can vary due to differences in tumor biology, growth patterns, and the developing brain in children.

• #16 Childhood Brain Tumors – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK535415/

  Pediatric brain tumors are the most common type of solid childhood cancer and only second to leukemia as a cause of pediatric malignancies. […] A combination of genetic and environmental factors is blamed to come into play in the pathogenesis of brain tumors. […] Family history may play a role in the etiology as many studies report an association of brain tumors and siblings. […] The parental age at birth may also play a role. Studies show that offspring are at high risk for brain cancer (astrocytoma and ependymoma) in women who are older than 40. […] High dose radiation has been linked to brain malignancies. Children who have received radiation for leukemia are known to be at risk for developing brain cancer. […] Further elaboration of the pathogenesis of brain tumor is beyond this quick review.

• #17 Brain Tumors in Children – Stanford Medicine Children’s Health

  https://deprod.stanfordchildrens.org/en/topic/default?id=brain-tumors-in-children-90-P02745

  The majority of brain tumors have abnormalities of genes involved in cell cycle control, causing uncontrolled cell growth. These abnormalities are caused by alterations directly in the genes, or by chromosome rearrangements that change the function of a gene. […] Patients with certain genetic conditions (neurofibromatosis, von Hippel-Lindau disease, Li-Fraumeni syndrome, and retinoblastoma) also have an increased risk for developing tumors of the central nervous system. […] Some chemicals may change the structure of a gene that protects the body from diseases and cancer. Research has been investigating parents of children with brain tumors and their past exposure to certain chemicals, including pesticides and petroleum products. […] Children who have received radiation therapy to the head as part of prior treatment for other malignancies are also at an increased risk for new brain tumors.

• #18 Brain Tumor in Children: Pediatric Brain Tumor, Childhood Brain Cancer

  https://my.clevelandclinic.org/health/diseases/6148-brain-tumor-childhood

  A pediatric brain tumor is a growth of abnormal brain cells in a child. A brain cell becomes abnormal when it undergoes genetic changes. The change in a specific gene of brain cells can cause the cell to form a tumor. […] A neoplasm forms when healthy cells multiply and grow out of control. Scientists don’t understand what causes cells to grow uncontrollably, but it may relate to genetic changes in a cell. […] There’s a link between some pediatric brain tumors and cancer syndromes (a collection of seemingly related health issues). Experts don’t fully understand this link yet.

• #19 All About Pediatric Gliomas (Low and High Grade) | OncoLink

  https://www.oncolink.org/cancers/brain-tumors/all-about-pediatric-gliomas-low-and-high-grade

  Gliomas are the most common type of brain tumor in both children and adults. About 3,540 brain and other CNS tumors will be diagnosed this year in children aged 0-14. […] In most cases, we do not know why children develop brain tumors. There are some syndromes or genetic mutations that we know increase a child’s risk of developing a glioma. These syndromes include Li-Fraumeni syndrome, Turcot syndrome, and neurofibromatosis. Children with neurofibromatosis are specifically at higher risk for developing optic pathway gliomas. Another syndrome, tuberous sclerosis, can also lead to an increased risk of a type of low-grade glioma called subependymal giant cell astrocytoma. […] When a child is diagnosed with a glioma, the histology, location and classification of the tumor will help guide the treatment of the tumor.

• #20 Brain Tumors in Children | Neurological Surgery

  https://neurosurgery.weillcornell.org/condition/brain-tumors-children

  What Causes a Pediatric Brain Tumor? Researchers dont know for sure what causes a brain tumor to develop in a child. Some brain tumors are associated with genetic conditions, such as neurofibromatosis, von Hippel-Lindau disease, Li-Fraumeni syndrome, and retinoblastoma. Some tumors may be caused by genetic mutations, by exposure to environmental toxins, or by previous radiation treatments for other cancers. […] A primary tumor is one that originated in the area in which it is found. Most pediatric brain tumors are primary. […] A malignant tumor is a cancerous growth that spreads and infiltrates into other brain tissue. The most common malignant tumor in children is called medulloblastoma (also called a primitive neuroectodermal tumor, or PNET). Treatments vary by the type and location of the tumor.

• #21 All About Pediatric Gliomas (Low and High Grade) | OncoLink

  https://www.oncolink.org/cancers/brain-tumors/all-about-pediatric-gliomas-low-and-high-grade

  Gliomas are the most common type of brain tumor in both children and adults. About 3,540 brain and other CNS tumors will be diagnosed this year in children aged 0-14. […] In most cases, we do not know why children develop brain tumors. There are some syndromes or genetic mutations that we know increase a child’s risk of developing a glioma. These syndromes include Li-Fraumeni syndrome, Turcot syndrome, and neurofibromatosis. Children with neurofibromatosis are specifically at higher risk for developing optic pathway gliomas. Another syndrome, tuberous sclerosis, can also lead to an increased risk of a type of low-grade glioma called subependymal giant cell astrocytoma. […] When a child is diagnosed with a glioma, the histology, location and classification of the tumor will help guide the treatment of the tumor.

• #22 Childhood Glioma (Including Astrocytoma) – NCI

  https://www.cancer.gov/types/brain/patient/childhood-glioma-astrocytoma

  Gliomas are caused by certain changes to the way glial cells function, especially how they grow and divide into new cells. Often, the exact cause of cell changes that lead to glioma is unknown. […] A risk factor is anything that increases the chance of getting a disease. Not every child with a risk factor will develop a glioma, and it will develop in some children who don’t have a known risk factor. Inherited genetic disorders that may be risk factors for glioma include: neurofibromatosis type 1, tuberous sclerosis. […] Tumor grading is based on World Health Organization (WHO) criteria. Tumor grade describes how abnormal the cancer cells look under a microscope, how quickly the tumor is likely to grow and spread within the central nervous system, and how likely the tumor is to come back after treatment.

• #23 Childhood Medulloblastoma & Other CNS Embryonal Tumors Treatment – NCI

  https://www.cancer.gov/types/brain/patient/child-cns-embryonal-treatment-pdq

  Medulloblastoma and other central nervous system (CNS) embryonal tumors may begin in embryonic (fetal) cells that remain in the brain after birth. […] Certain genetic conditions increase the risk of childhood medulloblastoma. […] Childhood medulloblastoma is caused by certain changes to the way brain cells function, especially how they grow and divide into new cells. Often, the exact cause of the cell changes is unknown. […] The risk for medulloblastoma is increased in people who have any of the following inherited diseases: Turcot syndrome, Rubinstein-Taybi syndrome, Nevoid basal cell carcinoma (Gorlin) syndrome, Li-Fraumeni syndrome, Fanconi anemia. […] Molecular testing checks for certain genes, proteins, or other molecules in a sample of tissue, blood, or bone marrow. Molecular tests also check for certain changes in a gene or chromosome that may cause or affect the chance of developing medulloblastoma, another type of embryonal tumor, or pineoblastoma.

• #24 Brain Tumors in Children | Neurological Surgery

  https://neurosurgery.weillcornell.org/condition/brain-tumors-children

  What Causes a Pediatric Brain Tumor? Researchers dont know for sure what causes a brain tumor to develop in a child. Some brain tumors are associated with genetic conditions, such as neurofibromatosis, von Hippel-Lindau disease, Li-Fraumeni syndrome, and retinoblastoma. Some tumors may be caused by genetic mutations, by exposure to environmental toxins, or by previous radiation treatments for other cancers. […] A primary tumor is one that originated in the area in which it is found. Most pediatric brain tumors are primary. […] A malignant tumor is a cancerous growth that spreads and infiltrates into other brain tissue. The most common malignant tumor in children is called medulloblastoma (also called a primitive neuroectodermal tumor, or PNET). Treatments vary by the type and location of the tumor.

• #25 Childhood Brain Tumors – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK535415/

  Pediatric brain tumors are the most common type of solid childhood cancer and only second to leukemia as a cause of pediatric malignancies. […] A combination of genetic and environmental factors is blamed to come into play in the pathogenesis of brain tumors. […] Family history may play a role in the etiology as many studies report an association of brain tumors and siblings. […] The parental age at birth may also play a role. Studies show that offspring are at high risk for brain cancer (astrocytoma and ependymoma) in women who are older than 40. […] High dose radiation has been linked to brain malignancies. Children who have received radiation for leukemia are known to be at risk for developing brain cancer. […] Further elaboration of the pathogenesis of brain tumor is beyond this quick review.

• #26 Brain Tumors in Children – Stanford Medicine Children’s Health

  https://deprod.stanfordchildrens.org/en/topic/default?id=brain-tumors-in-children-90-P02745

  The majority of brain tumors have abnormalities of genes involved in cell cycle control, causing uncontrolled cell growth. These abnormalities are caused by alterations directly in the genes, or by chromosome rearrangements that change the function of a gene. […] Patients with certain genetic conditions (neurofibromatosis, von Hippel-Lindau disease, Li-Fraumeni syndrome, and retinoblastoma) also have an increased risk for developing tumors of the central nervous system. […] Some chemicals may change the structure of a gene that protects the body from diseases and cancer. Research has been investigating parents of children with brain tumors and their past exposure to certain chemicals, including pesticides and petroleum products. […] Children who have received radiation therapy to the head as part of prior treatment for other malignancies are also at an increased risk for new brain tumors.

• #27 Brain Tumors in Children – Stanford Medicine Children’s Health

  https://deprod.stanfordchildrens.org/en/topic/default?id=brain-tumors-in-children-90-P02745

  The majority of brain tumors have abnormalities of genes involved in cell cycle control, causing uncontrolled cell growth. These abnormalities are caused by alterations directly in the genes, or by chromosome rearrangements that change the function of a gene. […] Patients with certain genetic conditions (neurofibromatosis, von Hippel-Lindau disease, Li-Fraumeni syndrome, and retinoblastoma) also have an increased risk for developing tumors of the central nervous system. […] Some chemicals may change the structure of a gene that protects the body from diseases and cancer. Research has been investigating parents of children with brain tumors and their past exposure to certain chemicals, including pesticides and petroleum products. […] Children who have received radiation therapy to the head as part of prior treatment for other malignancies are also at an increased risk for new brain tumors.

• #28 Brain Tumors in Children | Neurological Surgery

  https://neurosurgery.weillcornell.org/condition/brain-tumors-children

  What Causes a Pediatric Brain Tumor? Researchers dont know for sure what causes a brain tumor to develop in a child. Some brain tumors are associated with genetic conditions, such as neurofibromatosis, von Hippel-Lindau disease, Li-Fraumeni syndrome, and retinoblastoma. Some tumors may be caused by genetic mutations, by exposure to environmental toxins, or by previous radiation treatments for other cancers. […] A primary tumor is one that originated in the area in which it is found. Most pediatric brain tumors are primary. […] A malignant tumor is a cancerous growth that spreads and infiltrates into other brain tissue. The most common malignant tumor in children is called medulloblastoma (also called a primitive neuroectodermal tumor, or PNET). Treatments vary by the type and location of the tumor.

• #29 Childhood Brain Tumors – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK535415/

  Pediatric brain tumors are the most common type of solid childhood cancer and only second to leukemia as a cause of pediatric malignancies. […] A combination of genetic and environmental factors is blamed to come into play in the pathogenesis of brain tumors. […] Family history may play a role in the etiology as many studies report an association of brain tumors and siblings. […] The parental age at birth may also play a role. Studies show that offspring are at high risk for brain cancer (astrocytoma and ependymoma) in women who are older than 40. […] High dose radiation has been linked to brain malignancies. Children who have received radiation for leukemia are known to be at risk for developing brain cancer. […] Further elaboration of the pathogenesis of brain tumor is beyond this quick review.

• #30 Childhood Brain Tumors – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK535415/

  Pediatric brain tumors are the most common type of solid childhood cancer and only second to leukemia as a cause of pediatric malignancies. […] A combination of genetic and environmental factors is blamed to come into play in the pathogenesis of brain tumors. […] Family history may play a role in the etiology as many studies report an association of brain tumors and siblings. […] The parental age at birth may also play a role. Studies show that offspring are at high risk for brain cancer (astrocytoma and ependymoma) in women who are older than 40. […] High dose radiation has been linked to brain malignancies. Children who have received radiation for leukemia are known to be at risk for developing brain cancer. […] Further elaboration of the pathogenesis of brain tumor is beyond this quick review.

• #31 Frontiers | Pediatric brain tumors: A neuropathologist’s approach to the integrated diagnosis

  https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2023.1143363/full

  Pediatric CNS tumors, in particular, rely heavily on the integration of molecular data with histologic, clinical, and radiographic features to reach the most accurate diagnosis. […] The concept of incorporating molecular information with tumor histology to form an “integrated diagnosis” was introduced in the International Society of Neuropathology (ISN)-Haarlem guidelines in 2014 and formally adopted in the revised fourth edition of the WHO CNS tumor classification. […] Molecular testing is a key component to the integrated diagnosis and overall characterization of many CNS tumors. […] The formulation of an integrated diagnosis should take into account all pertinent clinical, radiographic, histologic, immunohistochemical, and molecular information. […] The ultimate goal of this integrated approach to the diagnosis of CNS tumors is to provide the most accurate representation of tumor biology and in turn, inform therapy selection and prognosis.

• #32 Frontiers | Pediatric brain tumors: A neuropathologist’s approach to the integrated diagnosis

  https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2023.1143363/full

  Pediatric CNS tumors, in particular, rely heavily on the integration of molecular data with histologic, clinical, and radiographic features to reach the most accurate diagnosis. […] The concept of incorporating molecular information with tumor histology to form an “integrated diagnosis” was introduced in the International Society of Neuropathology (ISN)-Haarlem guidelines in 2014 and formally adopted in the revised fourth edition of the WHO CNS tumor classification. […] Molecular testing is a key component to the integrated diagnosis and overall characterization of many CNS tumors. […] The formulation of an integrated diagnosis should take into account all pertinent clinical, radiographic, histologic, immunohistochemical, and molecular information. […] The ultimate goal of this integrated approach to the diagnosis of CNS tumors is to provide the most accurate representation of tumor biology and in turn, inform therapy selection and prognosis.

• #33 Molecular Insights into Pediatric Brain Tumors Have the Potential to Transform Therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4234174/

  These advances have been made possible by technologies capable of cataloging the sequence, copy number and expression of all genes. […] These studies have unmasked a common theme in pediatric brain tumors in which molecular discrete subtypes of each tumor likely arise from topographically discrete neural progenitor cells that are selectively susceptible to specific transforming mutations. […] The term medulloblastoma was originally used to describe all small round blue cell tumors of the cerebellum. […] The discovery of hSNF5/INI1 mutations in atypical teratoid/rhabdoid tumors (ATRT), provided the first firm evidence that not all tumors treated as medulloblastoma were the same disease. […] Studies conducted over the last ten years have identified distinct subtypes of medulloblastoma.

• #34 Molecular Insights into Pediatric Brain Tumors Have the Potential to Transform Therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4234174/

  High-throughput genomic technologies have shed light on the biologic heterogeneity of several pediatric brain tumors. […] The biology of the four common pediatric brain tumors namely medulloblastoma, ependymoma, high-grade glioma including diffuse intrinsic pontine glioma and low-grade glioma are highlighted in this CCR Focus article. […] The discovery that medulloblastoma consists of 4 different subgroups namely WNT, SHH, Group 3 and Group 4, each with distinct clinical and molecular features, has impacted the treatment of children with medulloblastoma. […] Developing and testing targeted therapies based on this new understanding remains a major challenge to the pediatric neuro-oncology community. […] The ability to analyze tissues on a genome-wide scale has transformed our understanding of childhood brain tumors.

• #35 Molecular Insights into Pediatric Brain Tumors Have the Potential to Transform Therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4234174/

  These discoveries were made possible by genomic technologies particularly those that measure gene expression. […] Alternative approaches to genomics to diagnose medulloblastoma subgroups are in development, and are likely to prove increasingly important to clinical management in light of the significant prognostic and treatment differences among subgroups. […] Initial cross-species genomic studies showed that ependymomas from different regions of the CNS share the gene expression profiles of neural stem cells (NSCs) in the corresponding region of the developing brain and spine. […] These data provided the first explanation for the regional heterogeneity of ependymoma and identified regionally discrete NSCs as candidate cells of origin of the different disease subtypes. […] Building on the understanding that ependymoma comprises regionally discrete subtypes, investigators performed whole genome sequencing of supratentorial and posterior fossa ependymomas with the aim of identifying driver mutations of these tumors.

• #36 Molecular Insights into Pediatric Brain Tumors Have the Potential to Transform Therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4234174/

  These discoveries were made possible by genomic technologies particularly those that measure gene expression. […] Alternative approaches to genomics to diagnose medulloblastoma subgroups are in development, and are likely to prove increasingly important to clinical management in light of the significant prognostic and treatment differences among subgroups. […] Initial cross-species genomic studies showed that ependymomas from different regions of the CNS share the gene expression profiles of neural stem cells (NSCs) in the corresponding region of the developing brain and spine. […] These data provided the first explanation for the regional heterogeneity of ependymoma and identified regionally discrete NSCs as candidate cells of origin of the different disease subtypes. […] Building on the understanding that ependymoma comprises regionally discrete subtypes, investigators performed whole genome sequencing of supratentorial and posterior fossa ependymomas with the aim of identifying driver mutations of these tumors.

• #37 Molecular Insights into Pediatric Brain Tumors Have the Potential to Transform Therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4234174/

  These discoveries were made possible by genomic technologies particularly those that measure gene expression. […] Alternative approaches to genomics to diagnose medulloblastoma subgroups are in development, and are likely to prove increasingly important to clinical management in light of the significant prognostic and treatment differences among subgroups. […] Initial cross-species genomic studies showed that ependymomas from different regions of the CNS share the gene expression profiles of neural stem cells (NSCs) in the corresponding region of the developing brain and spine. […] These data provided the first explanation for the regional heterogeneity of ependymoma and identified regionally discrete NSCs as candidate cells of origin of the different disease subtypes. […] Building on the understanding that ependymoma comprises regionally discrete subtypes, investigators performed whole genome sequencing of supratentorial and posterior fossa ependymomas with the aim of identifying driver mutations of these tumors.

• #38 Childhood brain tumors: current management, biological insights, and future directions in: Journal of Neurosurgery: Pediatrics Volume 23 Issue 3 (2019) Journals

  https://thejns.org/pediatrics/view/journals/j-neurosurg-pediatr/23/3/article-p261.xml

  Brain tumors are the most common solid tumors in children, and, unfortunately, many subtypes continue to have a suboptimal long-term outcome. […] During the last several years, however, remarkable advances in our understanding of the molecular underpinnings of these tumors have occurred as a result of high-resolution genomic, epigenetic, and transcriptomic profiling, which have provided insights for improved tumor categorization and molecularly directed therapies. […] The situation is even more complex for ependymoma, for which at least nine subsets of tumors have been described. […] Conversely, the majority of pilocytic astrocytomas appear to result from genetic changes that alter a single, therapeutically targetable molecular pathway. […] The feasibility of these goals has been dramatically augmented by the revolution in molecular biology during the last 5-10 years, which has yielded progressively more detailed insights into the genetic basis for virtually every type of childhood brain tumor.

• #39 Molecular Insights into Pediatric Brain Tumors Have the Potential to Transform Therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4234174/

  Both studies found very few single nucleotide variations, insertion/deletions, or focal (5 genes) copy number variations in ependymomas. […] This genomic disruption resulted in a novel translocation that fused a poorly characterized gene, C11orf95, to RELA, the principal effector of canonical NF-B signaling in 70% of supratentorial, but no posterior fossa or spinal ependymomas, making it the most recurrent genetic alteration in ependymoma. […] In light of the paucity of SNVs in ependymoma, Mack et al. studied the concept that posterior fossa ependymomas are driven by a dysregulated epigenome. […] These data suggest that drugs that target DNA CpG methylation, PRC2/EZH2, and/or histone deacetylase inhibitors could represent the first rational strategies for therapy of PFA-CIMP+ ependymoma.

• #40 Pediatric CNS Tumors – Free Sketchy Medical Lesson

  https://www.sketchy.com/medical-lessons/pediatric-cns-tumors

  In the pediatric population, CNS tumors primarily manifest infratentorially, a in contrast to adult CNS tumors which frequently present supratentorially. […] Risk factors include genetic syndromes like tuberous sclerosis and neurofibromatosis 1, as well as exposure to ionizing radiation. […] Pilocytic astrocytomas are the most common pediatric CNS tumor and are named for their hairlike projections observed under microscopy. These benign, grade 1 tumors frequently contain activating mutations in the BRAF gene, leading to abnormal cell growth. […] Medulloblastomas are the most common malignant CNS tumors in children. They originate from cells that are partially differentiated in the neuronal direction, staining positive for synaptophysin and neuron-specific enolase. […] Ependymomas are CNS tumors that arise from the ependymal cells lining the ventricular system. They most commonly grow from the roof of the 4th ventricle, which can cause intracranial hypertension due to obstructive hydrocephalus.

• #41 Childhood brain tumors: current management, biological insights, and future directions in: Journal of Neurosurgery: Pediatrics Volume 23 Issue 3 (2019) Journals

  https://thejns.org/pediatrics/view/journals/j-neurosurg-pediatr/23/3/article-p261.xml

  This information has not only helped to identify different subsets of tumors, now recognized by the World Health Organization (WHO) and warranting distinct approaches to treatment, but also indicated molecular targets that can be exploited in therapy for certain tumors, such as pilocytic astrocytomas, dramatically changing the therapeutic landscape during the last 2-3 years. […] While the above studies were in progress, a series of molecular analyses demonstrated that many pilocytic astrocytomas exhibit translocations or, less commonly, activating mutations of the BRAF gene, which may promote tumor development. […] Tumors lacking BRAF fusions or mutations often have alterations in other components of the mitogen-activated protein kinase (MAPK) signaling pathway, including NF1 mutations and RAF fusions.

• #42 Childhood brain tumors: current management, biological insights, and future directions in: Journal of Neurosurgery: Pediatrics Volume 23 Issue 3 (2019) Journals

  https://thejns.org/pediatrics/view/journals/j-neurosurg-pediatr/23/3/article-p261.xml

  Brain tumors are the most common solid tumors in children, and, unfortunately, many subtypes continue to have a suboptimal long-term outcome. […] During the last several years, however, remarkable advances in our understanding of the molecular underpinnings of these tumors have occurred as a result of high-resolution genomic, epigenetic, and transcriptomic profiling, which have provided insights for improved tumor categorization and molecularly directed therapies. […] The situation is even more complex for ependymoma, for which at least nine subsets of tumors have been described. […] Conversely, the majority of pilocytic astrocytomas appear to result from genetic changes that alter a single, therapeutically targetable molecular pathway. […] The feasibility of these goals has been dramatically augmented by the revolution in molecular biology during the last 5-10 years, which has yielded progressively more detailed insights into the genetic basis for virtually every type of childhood brain tumor.

• #43 Childhood brain tumors: current management, biological insights, and future directions in: Journal of Neurosurgery: Pediatrics Volume 23 Issue 3 (2019) Journals

  https://thejns.org/pediatrics/view/journals/j-neurosurg-pediatr/23/3/article-p261.xml

  This convergence of mutations on a single downstream pathway prompted interest in the targeted inhibition of MAPK signaling as a therapy for these tumors. […] In recent years, it has become increasingly clear that HGGs and DIPGs in children differ on a molecular basis from HGGs in adults, and many of the molecularly targeted strategies that have been employed based on adult data have little applicability in the pediatric context. […] Moreover, distinct subgroups of pediatric HGG and DIPG have been distinguished based on patterns of recurring mutations and epigenetic features, which associate with biological and clinical characteristics. […] Taken together, these data highlight the genomic and prognostic diversity among these tumors, provide insights for therapeutic stratification of patients into risk groups, and suggest molecular targets for therapy.

• #44 Childhood brain tumors: current management, biological insights, and future directions in: Journal of Neurosurgery: Pediatrics Volume 23 Issue 3 (2019) Journals

  https://thejns.org/pediatrics/view/journals/j-neurosurg-pediatr/23/3/article-p261.xml

  This convergence of mutations on a single downstream pathway prompted interest in the targeted inhibition of MAPK signaling as a therapy for these tumors. […] In recent years, it has become increasingly clear that HGGs and DIPGs in children differ on a molecular basis from HGGs in adults, and many of the molecularly targeted strategies that have been employed based on adult data have little applicability in the pediatric context. […] Moreover, distinct subgroups of pediatric HGG and DIPG have been distinguished based on patterns of recurring mutations and epigenetic features, which associate with biological and clinical characteristics. […] Taken together, these data highlight the genomic and prognostic diversity among these tumors, provide insights for therapeutic stratification of patients into risk groups, and suggest molecular targets for therapy.

• #45 Epigenomics and immunotherapeutic advances in pediatric brain tumors | npj Precision Oncology

  https://www.nature.com/articles/s41698-021-00173-4

  Molecular profiling has revealed significant differences between adult and pediatric brain tumors, despite having similar histology. […] The classification of pHGGs is based on molecular subgroups and significant clinical correlations (i.e., age, anatomical location, and prognosis). […] Overall, histone mutations represent slightly more than half of all childhood pHGG cases. […] The largest pHGG dataset to date was used in a retrospective study that revealed ten subgroups based on specific genes and processes and showed that histone mutations cosegregate with distinct modifications and downstream pathways. […] Epigenetic modifications are reversible structural alterations of the nucleic acid and histone proteins that constitute the nucleosome. […] The identification of genes that control epigenetic changes has produced novel targets for cancer treatments, particularly treatments for CNS tumors.

• #46 Childhood brain tumors: current management, biological insights, and future directions in: Journal of Neurosurgery: Pediatrics Volume 23 Issue 3 (2019) Journals

  https://thejns.org/pediatrics/view/journals/j-neurosurg-pediatr/23/3/article-p261.xml

  This convergence of mutations on a single downstream pathway prompted interest in the targeted inhibition of MAPK signaling as a therapy for these tumors. […] In recent years, it has become increasingly clear that HGGs and DIPGs in children differ on a molecular basis from HGGs in adults, and many of the molecularly targeted strategies that have been employed based on adult data have little applicability in the pediatric context. […] Moreover, distinct subgroups of pediatric HGG and DIPG have been distinguished based on patterns of recurring mutations and epigenetic features, which associate with biological and clinical characteristics. […] Taken together, these data highlight the genomic and prognostic diversity among these tumors, provide insights for therapeutic stratification of patients into risk groups, and suggest molecular targets for therapy.

• #47 Pediatric High-Grade Gliomas (HGG) – American Brain Tumor Association

  https://www.abta.org/tumor_types/pediatric-high-grade-gliomas-hgg/

  High-grade gliomas (HGG) are a group of aggressive brain and spinal cord tumors that occur in both children and adults and include such diagnoses as glioblastoma and anaplastic astrocytoma. […] These tumors characteristically grow (infiltrate) into normal central nervous system tissue, making them difficult to treat. […] The majority of HGG occurring in the midline of the brain or in the spinal cord have a characteristic mutation in the H3 protein known as H3K27M. In contrast, HGG occurring toward the edges of the brain have a related but distinct mutation known as H3G34R/V. HGG often have other mutations including BRAFV600E, IDH1/2, ATRX, TP53, or PDGFRA. HGG occurring in infants and toddlers may have fusions of two genes such as NTRK or ROS1.

• #48 Epigenomics and immunotherapeutic advances in pediatric brain tumors | npj Precision Oncology

  https://www.nature.com/articles/s41698-021-00173-4

  Molecular profiling has revealed significant differences between adult and pediatric brain tumors, despite having similar histology. […] The classification of pHGGs is based on molecular subgroups and significant clinical correlations (i.e., age, anatomical location, and prognosis). […] Overall, histone mutations represent slightly more than half of all childhood pHGG cases. […] The largest pHGG dataset to date was used in a retrospective study that revealed ten subgroups based on specific genes and processes and showed that histone mutations cosegregate with distinct modifications and downstream pathways. […] Epigenetic modifications are reversible structural alterations of the nucleic acid and histone proteins that constitute the nucleosome. […] The identification of genes that control epigenetic changes has produced novel targets for cancer treatments, particularly treatments for CNS tumors.

• #49 Molecular Insights into Pediatric Brain Tumors Have the Potential to Transform Therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4234174/

  Current treatment protocols include maximal-safe surgical resection while maintaining functional integrity, radiotherapy, and a variety of chemotherapy options. […] The heterogeneity seen, in terms of survival of pediatric patients with HGG, has yet to be explained. […] Next-generation sequencing studies published over the last 2 years have started to elucidate the unique mutational landscape of pediatric HGG. […] Several groups have shown that K27M mutations functionally inactivate the polycomb repressor complex 2 by entrapping EZH2, the main enzyme required to establish the repressive chromatin mark K27me3, thus conferring a dominant effect at the level of H3K27me on histones H3 and H3.3. […] Pediatric HGG is also very heterogeneous; the gross split between hemispheric tumors and midline tumors most likely indicates different cells of origin.

• #50 Origin of Childhood Brain Tumors Discovered

  https://www.genengnews.com/news/origin-of-childhood-brain-tumors-discovered/

  It has long been suspected that pediatric brain tumors originate prenatally. Now a team of scientists have used single-cell transcriptome atlas of >65,000 cells from embryonal pons and forebrain, two major tumor locations, to uncover that several types of highly aggressive and, ultimately, fatal pediatric brain tumors originate during brain development. Further, they show that the genetic event that triggers the disease happens in the very earliest phases of cellular development, most likely prenatally. […] We have determined that stalled development of progenitor cells in the pons and forebrain, where a large proportion of high-grade embryonal and pediatric tumors emerge, is responsible for several childhood brain cancers. […] New technologies allowing us to interrogate tumor cells each one at a time points to stalled development at the root of several high grade brain tumors in children.

• #51 Origin of Childhood Brain Tumors Discovered

  https://www.genengnews.com/news/origin-of-childhood-brain-tumors-discovered/

  It has long been suspected that pediatric brain tumors originate prenatally. Now a team of scientists have used single-cell transcriptome atlas of >65,000 cells from embryonal pons and forebrain, two major tumor locations, to uncover that several types of highly aggressive and, ultimately, fatal pediatric brain tumors originate during brain development. Further, they show that the genetic event that triggers the disease happens in the very earliest phases of cellular development, most likely prenatally. […] We have determined that stalled development of progenitor cells in the pons and forebrain, where a large proportion of high-grade embryonal and pediatric tumors emerge, is responsible for several childhood brain cancers. […] New technologies allowing us to interrogate tumor cells each one at a time points to stalled development at the root of several high grade brain tumors in children.

• #52 Origin of Childhood Brain Tumors Discovered

  https://www.genengnews.com/news/origin-of-childhood-brain-tumors-discovered/

  The cornerstone to fighting these conditions is to identify the biological process at work, which is what our research has achieved. […] Current evidence thus supports a common etiological model for these tumors, where genetic alterations in vulnerable cell types disrupt developmental gene expression programs, ultimately leading to oncogenesis. The findings identify impaired differentiation of specific neural progenitors as a common mechanism underlying these pediatric cancers and provide a rational framework for future modeling and therapeutic interventions.

• #53 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Identifying-Early-Childhood-Brain-Cancer.aspx

  Second, to leukemia, a pediatric brain tumor is the most common form of malignancy in children. […] Studies have identified that certain normal brain cells, which appear much earlier than they are expected in fetal development, undergo neoplastic transformation to develop malignant brain tumors later in life. […] Despite being the leading cause of non-accidental death in children, the mechanism of the childhood brain cancer development and progression is still unclear. […] In this context, a recent study using mouse models has identified certain normal cells that are believed to undergo the neoplastic transformation process and develop childhood brain cancers. These cells initially appear in the embryonic development stage much earlier than they are expected. […] The investigation of more than 30 types of cells in the mouse cerebellum has led to the identification of certain normal cells that are predisposed to neoplastic transformation.

• #54 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Identifying-Early-Childhood-Brain-Cancer.aspx

  The study findings have revealed that specific cell populations are involved in developing different types of childhood brain cancers. […] Another very interesting study has revealed that genetic mutations that are responsible for childhood brain cancer development occur in the very early stages of fetal development. The study has identified specific cell populations in the pons and forebrain (brain areas where high-grade brain tumors develop) that undergo growth arrest rather than developing normally. These cells are ultimately transformed into cancerous cells.

• #55 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.

• #56 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.

• #57 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.

• #58 Autophagy in brain tumors: molecular mechanisms, challenges, and therapeutic opportunities | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-06063-0

  Autophagy plays a crucial role in the development of diseases, particularly human cancers, with actions that can either promote survival or induce cell death. […] Hence, having knowledge of the role of molecular processes in the advancement of brain tumors is enlightening, and the current review specifically examines the role of autophagy. […] Autophagy can control the advancement of different types of brain tumors like glioblastoma, glioma, and ependymoma, demonstrating its potential for treatment. […] Autophagy mechanisms can influence metastasis and drug resistance in glioblastoma, and there is a complex interplay between autophagy and cellular responses to stress like hypoxia and starvation. […] Autophagy can inhibit the growth of brain tumors by promoting apoptosis. […] The present study focuses on investigating the role of autophagy in the advancement of brain tumors, with an emphasis on the molecular pathways that control this mechanism.

• #59 Autophagy in brain tumors: molecular mechanisms, challenges, and therapeutic opportunities | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-06063-0

  Autophagy plays a crucial role in the development of diseases, particularly human cancers, with actions that can either promote survival or induce cell death. […] Hence, having knowledge of the role of molecular processes in the advancement of brain tumors is enlightening, and the current review specifically examines the role of autophagy. […] Autophagy can control the advancement of different types of brain tumors like glioblastoma, glioma, and ependymoma, demonstrating its potential for treatment. […] Autophagy mechanisms can influence metastasis and drug resistance in glioblastoma, and there is a complex interplay between autophagy and cellular responses to stress like hypoxia and starvation. […] Autophagy can inhibit the growth of brain tumors by promoting apoptosis. […] The present study focuses on investigating the role of autophagy in the advancement of brain tumors, with an emphasis on the molecular pathways that control this mechanism.

• #60 Autophagy in brain tumors: molecular mechanisms, challenges, and therapeutic opportunities | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-06063-0

  Autophagy plays a crucial role in the development of diseases, particularly human cancers, with actions that can either promote survival or induce cell death. […] Hence, having knowledge of the role of molecular processes in the advancement of brain tumors is enlightening, and the current review specifically examines the role of autophagy. […] Autophagy can control the advancement of different types of brain tumors like glioblastoma, glioma, and ependymoma, demonstrating its potential for treatment. […] Autophagy mechanisms can influence metastasis and drug resistance in glioblastoma, and there is a complex interplay between autophagy and cellular responses to stress like hypoxia and starvation. […] Autophagy can inhibit the growth of brain tumors by promoting apoptosis. […] The present study focuses on investigating the role of autophagy in the advancement of brain tumors, with an emphasis on the molecular pathways that control this mechanism.

• #61 Autophagy in brain tumors: molecular mechanisms, challenges, and therapeutic opportunities | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-06063-0

  Autophagy plays a crucial role in the development of diseases, particularly human cancers, with actions that can either promote survival or induce cell death. […] Hence, having knowledge of the role of molecular processes in the advancement of brain tumors is enlightening, and the current review specifically examines the role of autophagy. […] Autophagy can control the advancement of different types of brain tumors like glioblastoma, glioma, and ependymoma, demonstrating its potential for treatment. […] Autophagy mechanisms can influence metastasis and drug resistance in glioblastoma, and there is a complex interplay between autophagy and cellular responses to stress like hypoxia and starvation. […] Autophagy can inhibit the growth of brain tumors by promoting apoptosis. […] The present study focuses on investigating the role of autophagy in the advancement of brain tumors, with an emphasis on the molecular pathways that control this mechanism.

• #62 Autophagy in brain tumors: molecular mechanisms, challenges, and therapeutic opportunities | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-06063-0

  Hence, autophagy has the ability to control advancement of GBM. […] Autophagy plays a crucial role in treating cancer by blocking the start of tumors and destroying cancer cells as they advance. […] Autophagy could potentially stop the growth of tumors by triggering apoptosis through the ATG protein. […] The regulation of cell death mechanisms, including autophagy, is one of the ways in which 3beta androstene 17alpha diol (17alpha-AED) exerts its anti-cancer effects on glioma. […] The modulation of autophagy as a potential factor in the advancement of brain tumors and its manipulation (whether triggered or blocked) could be considered in the therapy for these malignancies. […] The role of autophagy in the progression of brain tumors. […] The activation of autophagy by certain experimental treatments for glioma may play a role in either cell death or survival, but its exact impact is still not completely clear and varies depending on the situation.

• #63 Autophagy in brain tumors: molecular mechanisms, challenges, and therapeutic opportunities | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-06063-0

  Autophagy is vital for the survival of tumor cells in the hypoxic glioma region and contributes to its aggressiveness. […] Autophagy plays a crucial role in treating cancer by blocking the start of tumors and destroying cancer cells as they advance. […] Autophagy has also been extensively recorded in controlling the development of different brain tumors including medulloblastoma. […] The inhibition of autophagy with 3-MA has proven advantageous for protecting astrocytoma cells from the toxicity induced by pyocyanin and 1-hydroxyphenazine. […] The data demonstrates that enhancing nucleophagy is essential in reducing the tumorigenicity of ependymoma, as shown by the discovery that mTOR inhibitors can reduce tumor growth in vivo by restoring nucleophagy. […] This perspective suggests that triggering autophagy might offer a treatment option for ependymoma.

• #64

  https://journals.lww.com/tnoc/fulltext/2020/03030/mechanisms_of_telomere_maintenance_in_pediatric.4.aspx

  Recent advances in genetic and molecular characterization of telomere maintenance mechanisms (TMMs) highlighted their strong relationship with cancer pathogenesis; neoplastic cells rely on two mechanisms to maintain telomere length and escape from replicative senescence: (a) reactivation of telomerase expression and (b) activation of alternative lengthening of telomere (ALT). […] Cancer cells overcome this limit and escape from replicative senescence by activating a TMM, necessary for unlimited replication and immortalization of the neoplastic cells, preventing genetic instability associated with critical telomere shortening. […] Neoplastic cells rely on two mechanisms to elongate telomeres: (a) reactivation of telomerase expression and (b) activation of alternative lengthening of telomere (ALT).

• #65

  https://journals.lww.com/tnoc/fulltext/2020/03030/mechanisms_of_telomere_maintenance_in_pediatric.4.aspx

  Recent advances in genetic and molecular characterization of telomere maintenance mechanisms (TMMs) highlighted their strong relationship with cancer pathogenesis; neoplastic cells rely on two mechanisms to maintain telomere length and escape from replicative senescence: (a) reactivation of telomerase expression and (b) activation of alternative lengthening of telomere (ALT). […] Cancer cells overcome this limit and escape from replicative senescence by activating a TMM, necessary for unlimited replication and immortalization of the neoplastic cells, preventing genetic instability associated with critical telomere shortening. […] Neoplastic cells rely on two mechanisms to elongate telomeres: (a) reactivation of telomerase expression and (b) activation of alternative lengthening of telomere (ALT).

• #66

  https://journals.lww.com/tnoc/fulltext/2020/03030/mechanisms_of_telomere_maintenance_in_pediatric.4.aspx

  The main hallmarks and genetic alterations involved in the ALT activation are shown in Figure 2. […] Telomerase-dependent TMM is a common mechanism in SHH-medulloblastomas and ependymomas, which could potentially benefit from antitelomerase therapies, while ALT-dependent TMM is more frequently activated in -thalassemia/mental retardation syndrome X-linked/H3.3-mutated pediatric high-grade gliomas, metastatic medulloblastomas, and choroid plexus tumors, which could potentially be treated with ALT-targeted drugs. […] Telomerase-dependent TMM appears to be a common mechanism in SHH-medulloblastomas, associated with older patients and TERTp mutations, and in pediatric ependymomas, rarely associated with TERTp mutations while more frequently induced by TERTp hypermethylation or other alterations; these patients could potentially benefit in the future from antitelomerase therapies. […] Further studies are necessary to better elucidate other genetic and epigenetic alterations associated with these mechanisms, to identify the best reproducible and reliable methods for TMMs detection in clinical practice, and to evaluate the effects of targeted therapies.

• #67

  https://journals.lww.com/tnoc/fulltext/2020/03030/mechanisms_of_telomere_maintenance_in_pediatric.4.aspx

  The aim of this review was to describe the incidence of TMM via telomerase or ALT in different histological/molecular subtypes of pediatric brain tumors (PBTs), since telomerase-targeted and ALT-targeted therapies are currently tested in preclinical studies and could constitute a promising approach for certain tumor types. […] The prevalence of ALT in cancers is not uniform across the different tumor types; Heaphy et al. have systematically analyzed the presence of ALT phenotype in 6110 primary tumors from 94 different cancer subtypes by telomere-specific fluorescence in situ hybridization, showing ALT activation in 3.73% (228/6110) of all tumors, arising from the bladder, cervix, endometrium, esophagus, kidney, liver, central nervous system (CNS), and lung. […] It has been shown that ALT is frequently associated with loss-of-function mutations in the chromatin remodeling genes, -thalassemia/mental retardation syndrome X-linked (ATRX) and death domain-associated protein (DAXX).

• #68

  https://journals.lww.com/tnoc/fulltext/2020/03030/mechanisms_of_telomere_maintenance_in_pediatric.4.aspx

  The main hallmarks and genetic alterations involved in the ALT activation are shown in Figure 2. […] Telomerase-dependent TMM is a common mechanism in SHH-medulloblastomas and ependymomas, which could potentially benefit from antitelomerase therapies, while ALT-dependent TMM is more frequently activated in -thalassemia/mental retardation syndrome X-linked/H3.3-mutated pediatric high-grade gliomas, metastatic medulloblastomas, and choroid plexus tumors, which could potentially be treated with ALT-targeted drugs. […] Telomerase-dependent TMM appears to be a common mechanism in SHH-medulloblastomas, associated with older patients and TERTp mutations, and in pediatric ependymomas, rarely associated with TERTp mutations while more frequently induced by TERTp hypermethylation or other alterations; these patients could potentially benefit in the future from antitelomerase therapies. […] Further studies are necessary to better elucidate other genetic and epigenetic alterations associated with these mechanisms, to identify the best reproducible and reliable methods for TMMs detection in clinical practice, and to evaluate the effects of targeted therapies.

• #69 Drug Repurposing in Pediatric Brain Tumors: Posterior Fossa Ependymoma and Diffuse Midline Glioma under the Looking Glass

  https://www.imrpress.com/journal/FBL/28/4/10.31083/j.fbl2804077/htm

  The development of a new drug, from de novo discovery to final registration, requires an estimated time frame of 13–15 years, and an average expenditure of 2–3 billion US dollars. To expedite this process, drug repositioning is an attractive approach as it allows the use of approved or investigational drugs for indications other than their originally intended use. […] Recently, mutually supportive interactions between tumor cells and the surrounding tumor microenvironments (TMEs) have increasingly been acknowledged as a driving force for both tumor progression and response to therapy. […] In recent years, multiomics approaches have fueled significant advancements in our understanding of the molecular basis of pediatric neuro-oncogenesis. These efforts have allowed for robust stratification of histological tumor entities in clinically relevant molecular groups, which differ in epidemiologic, clinical, and biological profiles, and support the need for distinct treatment interventions.

• #70 New hope for children with brain tumors — Harvard Gazette

  https://news.harvard.edu/gazette/story/2017/01/new-hope-for-children-with-brain-tumors/

  Precision medicine in which diagnosis and treatments are keyed to the genetic susceptibilities of individual cancers can play a major role in treating children with brain tumors, suggests a study by investigators at Dana-Farber/Boston Childrens Cancer and Blood Disorders Center. […] In the largest clinical study to date of genetic abnormalities in pediatric brain tumors, researchers performed clinical testing on more than 200 tumor samples and found that a majority had genetic irregularities that could influence how the disease was diagnosed and/or treated with approved drugs or agents being evaluated in clinical trials. […] The importance of genomic profiling in the diagnosis and treatment of pediatric brain cancers is reflected in the World Health Organizations recent decision to classify such tumors by the genetic alterations within them, rather than by broad tumor type says study co-senior author Susan Chi of Dana-Farber/Boston Childrens, an assistant professor of pediatrics at HMS. Targeted therapies are likely to be most effective when theyre matched to specific abnormalities within tumor cells. Our findings show that precision medicine for pediatric brain tumors can now be a reality.

• #71 New hope for children with brain tumors — Harvard Gazette

  https://news.harvard.edu/gazette/story/2017/01/new-hope-for-children-with-brain-tumors/

  Precision medicine in which diagnosis and treatments are keyed to the genetic susceptibilities of individual cancers can play a major role in treating children with brain tumors, suggests a study by investigators at Dana-Farber/Boston Childrens Cancer and Blood Disorders Center. […] In the largest clinical study to date of genetic abnormalities in pediatric brain tumors, researchers performed clinical testing on more than 200 tumor samples and found that a majority had genetic irregularities that could influence how the disease was diagnosed and/or treated with approved drugs or agents being evaluated in clinical trials. […] The importance of genomic profiling in the diagnosis and treatment of pediatric brain cancers is reflected in the World Health Organizations recent decision to classify such tumors by the genetic alterations within them, rather than by broad tumor type says study co-senior author Susan Chi of Dana-Farber/Boston Childrens, an assistant professor of pediatrics at HMS. Targeted therapies are likely to be most effective when theyre matched to specific abnormalities within tumor cells. Our findings show that precision medicine for pediatric brain tumors can now be a reality.

• #72 New hope for children with brain tumors — Harvard Gazette

  https://news.harvard.edu/gazette/story/2017/01/new-hope-for-children-with-brain-tumors/

  Precision medicine in which diagnosis and treatments are keyed to the genetic susceptibilities of individual cancers can play a major role in treating children with brain tumors, suggests a study by investigators at Dana-Farber/Boston Childrens Cancer and Blood Disorders Center. […] In the largest clinical study to date of genetic abnormalities in pediatric brain tumors, researchers performed clinical testing on more than 200 tumor samples and found that a majority had genetic irregularities that could influence how the disease was diagnosed and/or treated with approved drugs or agents being evaluated in clinical trials. […] The importance of genomic profiling in the diagnosis and treatment of pediatric brain cancers is reflected in the World Health Organizations recent decision to classify such tumors by the genetic alterations within them, rather than by broad tumor type says study co-senior author Susan Chi of Dana-Farber/Boston Childrens, an assistant professor of pediatrics at HMS. Targeted therapies are likely to be most effective when theyre matched to specific abnormalities within tumor cells. Our findings show that precision medicine for pediatric brain tumors can now be a reality.

• #73 Childhood brain tumors: current management, biological insights, and future directions in: Journal of Neurosurgery: Pediatrics Volume 23 Issue 3 (2019) Journals

  https://thejns.org/pediatrics/view/journals/j-neurosurg-pediatr/23/3/article-p261.xml

  This convergence of mutations on a single downstream pathway prompted interest in the targeted inhibition of MAPK signaling as a therapy for these tumors. […] In recent years, it has become increasingly clear that HGGs and DIPGs in children differ on a molecular basis from HGGs in adults, and many of the molecularly targeted strategies that have been employed based on adult data have little applicability in the pediatric context. […] Moreover, distinct subgroups of pediatric HGG and DIPG have been distinguished based on patterns of recurring mutations and epigenetic features, which associate with biological and clinical characteristics. […] Taken together, these data highlight the genomic and prognostic diversity among these tumors, provide insights for therapeutic stratification of patients into risk groups, and suggest molecular targets for therapy.

• #74 Pediatric brain tumors: A molecular era – CHOC Pediatrica

  https://care.choc.org/pediatric-brain-tumors-a-molecular-era/

  While incidents of pediatric cancer have gone up in recent decades, the mortality rate has gone down. […] Recently, we learned that most brain tumors were driven genetically in children. […] Dr. Sato briefly discussed new kinds of treatments that are becoming available. They include targeted gene therapies, vaccines and even cannabidiol. […] On the genetic level, there are several promising avenues to explore in treating tumors. One, a MEK inhibitor, may help keep abnormal cells from growing.

• #75 Neurobiology and Brain Tumor Program | St. Jude Research

  https://www.stjude.org/research/comprehensive-cancer-center/research/neurobiology-and-brain-tumor-program.html

  They identified an oncohistone mutation that affects growth of the deadliest HGG, called high-grade diffuse midline glioma (DMG); furthermore, this mutation shows potential as a therapeutic target. […] The NBTP has advanced CAR T-cell therapy in a variety of ways such as: identified a promising antigen for relapsed or refractory brain tumors such as MB and DMB; enhanced antitumor activity and proliferative capacity of CAR T cells; discovered new molecular targets. […] Understanding the relationship between disease and prognosis is an area of active research in the NBTP. […] The ability to molecularly stratify patients (and disease) based on genetic characteristics and use this information to inform treatment strategies and predict prognoses is transformative. […] NBTP members have used a variety of state-of-the-art molecular stratification approaches to more comprehensively understand several pediatric brain tumors.

• #76 Technology offers new insights into pediatric brain tumors • healthcare-in-europe.com

  https://healthcare-in-europe.com/en/news/technology-pediatric-brain-tumors.html

  Embryonal tumors of the central nervous system (CNS) are a class of malignant tumors composed of embryonal neuroepithelial cells predominantly found in children. […] Epigenetic studies, particularly DNA methylation profiling, have an increasing importance in the classification of brain tumors and new tumor types delineation. […] The BRD4 gene (Bromodomain Containing 4) acts in transcriptional regulation and development, as well as maintaining the pluripotency of stem cells, and its dysregulation has been associated with different types of cancer, as it contributes to cell proliferation and tumor progression. […] The LEUTX gene (Leucine Twenty Homeobox) plays a role in embryonic development and regulation of early cell differentiation. […] Although the sample size is small, preliminary results indicated that these tumors are clinically aggressive, requiring personalized treatment strategies that combine chemotherapy with total surgical removal of the tumor. […] It is worth noting that small molecule BRD4 inhibitors and BRD4 degraders have shown promising results in preliminary studies in hematological and solid malignancies and may represent a future therapeutic avenue for these aggressive CNS tumors.

• #77 Molecular Insights into Pediatric Brain Tumors Have the Potential to Transform Therapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4234174/

  Both studies found very few single nucleotide variations, insertion/deletions, or focal (5 genes) copy number variations in ependymomas. […] This genomic disruption resulted in a novel translocation that fused a poorly characterized gene, C11orf95, to RELA, the principal effector of canonical NF-B signaling in 70% of supratentorial, but no posterior fossa or spinal ependymomas, making it the most recurrent genetic alteration in ependymoma. […] In light of the paucity of SNVs in ependymoma, Mack et al. studied the concept that posterior fossa ependymomas are driven by a dysregulated epigenome. […] These data suggest that drugs that target DNA CpG methylation, PRC2/EZH2, and/or histone deacetylase inhibitors could represent the first rational strategies for therapy of PFA-CIMP+ ependymoma.

• #78 Pediatric Brain Tumors | SpringerLink

  https://link.springer.com/10.1007/978-3-662-43559-5_156

  Tumors of the central nervous system are the most common type of solid neoplasm found in children and are second only to leukemia in overall cancer frequency. […] The contribution of molecular genetics to brain tumor diagnostics is an ever-expanding field that has potential to significantly impact classification, prognosis, and therapeutic management of most CNS tumors. […] Different treatment modalities such as surgery, radiotherapy, and chemotherapy are widely used management entities; however, morbidity and mortality in pediatric brain tumors remains high. Novel targeted therapies and approaches to multidisciplinary treatment strategies are required if progress is to be achieved to cure most pediatric brain tumors.

• #79 Brain tumor – children: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000768.htm

  A brain tumor is a group (mass) of abnormal cells that grow in the brain. […] The cause of primary brain tumors is often unknown. Some primary brain tumors are related to other syndromes or can run in a family. […] Brain tumors can directly kill brain cells. They can also damage cells by pushing on other parts of the brain. This leads to swelling and increased pressure inside the skull. […] Treatment depends on the size and type of tumor and the child’s general health. The goals of treatment may be to cure the tumor, relieve symptoms, and improve brain function or the child’s comfort. […] Long-term brain and nervous system problems may result from the tumor itself or from treatment. Children may have problems with attention, focus, or memory. They may also have problems processing information, planning, insight, or initiative or desire to do things. […] Children younger than age 7, especially younger than age 3, seem to be at greatest risk of these complications.

• #80 Brain tumor – children: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000768.htm

  A brain tumor is a group (mass) of abnormal cells that grow in the brain. […] The cause of primary brain tumors is often unknown. Some primary brain tumors are related to other syndromes or can run in a family. […] Brain tumors can directly kill brain cells. They can also damage cells by pushing on other parts of the brain. This leads to swelling and increased pressure inside the skull. […] Treatment depends on the size and type of tumor and the child’s general health. The goals of treatment may be to cure the tumor, relieve symptoms, and improve brain function or the child’s comfort. […] Long-term brain and nervous system problems may result from the tumor itself or from treatment. Children may have problems with attention, focus, or memory. They may also have problems processing information, planning, insight, or initiative or desire to do things. […] Children younger than age 7, especially younger than age 3, seem to be at greatest risk of these complications.

• #81 Autophagy in brain tumors: molecular mechanisms, challenges, and therapeutic opportunities | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-06063-0

  The findings suggest that dysregulation of autophagy control may be responsible for oligodendroglial pathology. […] The relationship between ILK and AKT regulates the miR-21 expression in vertebular schwannoma and meningioma. […] The effectiveness of Farnesol for treating optic nerve meningioma was assessed by studying its ability to inhibit cell growth in HBL-52 cells. […] The failure to treat brain tumors is due to the ineffectiveness of conventional methods in causing cell death. […] The new therapeutics can be developed based on targeting autophagy for accelerating therapy and improving response to conventional therapeutics, including chemotherapy. […] Since autophagy has both carcinogenic and anti-carcinogenic functions, the regulation of autophagy should be performed in a cautious way. […] Therefore, both induction and suppression of autophagy have been followed for the treatment of cancer.

• #82 Autophagy in brain tumors: molecular mechanisms, challenges, and therapeutic opportunities | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-06063-0

  The findings suggest that dysregulation of autophagy control may be responsible for oligodendroglial pathology. […] The relationship between ILK and AKT regulates the miR-21 expression in vertebular schwannoma and meningioma. […] The effectiveness of Farnesol for treating optic nerve meningioma was assessed by studying its ability to inhibit cell growth in HBL-52 cells. […] The failure to treat brain tumors is due to the ineffectiveness of conventional methods in causing cell death. […] The new therapeutics can be developed based on targeting autophagy for accelerating therapy and improving response to conventional therapeutics, including chemotherapy. […] Since autophagy has both carcinogenic and anti-carcinogenic functions, the regulation of autophagy should be performed in a cautious way. […] Therefore, both induction and suppression of autophagy have been followed for the treatment of cancer.

• #83 Key Culprit in Pediatric Brain Cancer Uncovered | University of Pittsburgh

  https://www.neurosurgery.pitt.edu/news/key-culprit-pediatric-brain-cancer-uncovered

  Brain tumors are the leading cause of cancer death in children. The most common malignant childrens brain tumor is medulloblastoma. […] New research from the University of Pittsburgh School of Medicine Department of Neurological Surgery and UPMC Childrens Hospital of Pittsburgh pinpoints a key culprit controlling cancer cell metastasis and provides a potential new therapy for treating these tumors in the future. […] Developing drugs that can dismantle tumor cells to obtain this capability might pave the way for new and effective treatments. […] Longstanding challenges that we face in the field include understanding how tumors are able to spread and how we can stop tumor metastasis in basic science and clinical treatment. […] To find out how medulloblastoma cells metastasize, Dr. Hu and his research colleagues have leveraged medulloblastoma patient data and experimental mouse data to identify a gene, called SMARCD3 or BAF60C, whose levels are significantly higher in disseminated tumors than those in nondisseminated tumors.

• #84 Key Culprit in Pediatric Brain Cancer Uncovered | University of Pittsburgh

  https://www.neurosurgery.pitt.edu/news/key-culprit-pediatric-brain-cancer-uncovered

  Brain tumors are the leading cause of cancer death in children. The most common malignant childrens brain tumor is medulloblastoma. […] New research from the University of Pittsburgh School of Medicine Department of Neurological Surgery and UPMC Childrens Hospital of Pittsburgh pinpoints a key culprit controlling cancer cell metastasis and provides a potential new therapy for treating these tumors in the future. […] Developing drugs that can dismantle tumor cells to obtain this capability might pave the way for new and effective treatments. […] Longstanding challenges that we face in the field include understanding how tumors are able to spread and how we can stop tumor metastasis in basic science and clinical treatment. […] To find out how medulloblastoma cells metastasize, Dr. Hu and his research colleagues have leveraged medulloblastoma patient data and experimental mouse data to identify a gene, called SMARCD3 or BAF60C, whose levels are significantly higher in disseminated tumors than those in nondisseminated tumors.

• #85 Key Culprit in Pediatric Brain Cancer Uncovered | University of Pittsburgh

  https://www.neurosurgery.pitt.edu/news/key-culprit-pediatric-brain-cancer-uncovered

  Brain tumors are the leading cause of cancer death in children. The most common malignant childrens brain tumor is medulloblastoma. […] New research from the University of Pittsburgh School of Medicine Department of Neurological Surgery and UPMC Childrens Hospital of Pittsburgh pinpoints a key culprit controlling cancer cell metastasis and provides a potential new therapy for treating these tumors in the future. […] Developing drugs that can dismantle tumor cells to obtain this capability might pave the way for new and effective treatments. […] Longstanding challenges that we face in the field include understanding how tumors are able to spread and how we can stop tumor metastasis in basic science and clinical treatment. […] To find out how medulloblastoma cells metastasize, Dr. Hu and his research colleagues have leveraged medulloblastoma patient data and experimental mouse data to identify a gene, called SMARCD3 or BAF60C, whose levels are significantly higher in disseminated tumors than those in nondisseminated tumors.

• #86 Key Culprit in Pediatric Brain Cancer Uncovered | University of Pittsburgh

  https://www.neurosurgery.pitt.edu/news/key-culprit-pediatric-brain-cancer-uncovered

  The research team further showed how SMARCD3/BAF60C hijacks neurodevelopmental signaling to promote tumor cell spreading. […] Based on the new findings, the investigators also tested a drug, which was approved to treat leukemia in the clinic, and showed that this drug prefers to kill disseminated tumors that have higher levels of SMARCD3/BAF60C. […] This cancer neuroscience approach helped us to pinpoint the fundamental mechanisms, which may allow us to develop safe, effective, and personalized medical treatments for children with this devastating brain cancer.

• #87

  https://www.scienceboard.net/index.aspx?sec=log&log=true&itemID=5280

  Immune homing mechanism enables targeted drug delivery to pediatric brain tumors in mice. […] By directing therapies to the tumor, physicians could deliver higher doses to the affected tissues without harming healthy cells. […] The blood-brain barrier, which controls which molecules enter the brain, makes it hard to achieve such targeting. […] The formulation, which was enhanced by the administration of very low-dose radiation, could get more of the drug to the brain and less to the bone, thereby make the risk-benefit profile more favorable. […] We show that we can more successfully deliver lower doses of the drug in a more effective manner to the specific sites of tumor within the brain, while sparing the bone toxicity that is seen in younger patients. […] SHH medulloblastoma accounts for around 25% of cases; clinical trials suggest that vismodegib may help some patients, although on-target bone toxicities are a problem. […] By pairing vismodegib with a nanoparticle that targets P-selectin, a transmembrane protein expressed on epithelial cells, Raju and his collaborators enhanced mouse survival without causing the bone toxicity that is normally associated with the SHH pathway inhibitor.

• #88

  https://www.scienceboard.net/index.aspx?sec=log&log=true&itemID=5280

  Immune homing mechanism enables targeted drug delivery to pediatric brain tumors in mice. […] By directing therapies to the tumor, physicians could deliver higher doses to the affected tissues without harming healthy cells. […] The blood-brain barrier, which controls which molecules enter the brain, makes it hard to achieve such targeting. […] The formulation, which was enhanced by the administration of very low-dose radiation, could get more of the drug to the brain and less to the bone, thereby make the risk-benefit profile more favorable. […] We show that we can more successfully deliver lower doses of the drug in a more effective manner to the specific sites of tumor within the brain, while sparing the bone toxicity that is seen in younger patients. […] SHH medulloblastoma accounts for around 25% of cases; clinical trials suggest that vismodegib may help some patients, although on-target bone toxicities are a problem. […] By pairing vismodegib with a nanoparticle that targets P-selectin, a transmembrane protein expressed on epithelial cells, Raju and his collaborators enhanced mouse survival without causing the bone toxicity that is normally associated with the SHH pathway inhibitor.

• #89

  https://www.scienceboard.net/index.aspx?sec=log&log=true&itemID=5280

  Immune homing mechanism enables targeted drug delivery to pediatric brain tumors in mice. […] By directing therapies to the tumor, physicians could deliver higher doses to the affected tissues without harming healthy cells. […] The blood-brain barrier, which controls which molecules enter the brain, makes it hard to achieve such targeting. […] The formulation, which was enhanced by the administration of very low-dose radiation, could get more of the drug to the brain and less to the bone, thereby make the risk-benefit profile more favorable. […] We show that we can more successfully deliver lower doses of the drug in a more effective manner to the specific sites of tumor within the brain, while sparing the bone toxicity that is seen in younger patients. […] SHH medulloblastoma accounts for around 25% of cases; clinical trials suggest that vismodegib may help some patients, although on-target bone toxicities are a problem. […] By pairing vismodegib with a nanoparticle that targets P-selectin, a transmembrane protein expressed on epithelial cells, Raju and his collaborators enhanced mouse survival without causing the bone toxicity that is normally associated with the SHH pathway inhibitor.

• #90

  https://www.scienceboard.net/index.aspx?sec=log&log=true&itemID=5280

  Immune homing mechanism enables targeted drug delivery to pediatric brain tumors in mice. […] By directing therapies to the tumor, physicians could deliver higher doses to the affected tissues without harming healthy cells. […] The blood-brain barrier, which controls which molecules enter the brain, makes it hard to achieve such targeting. […] The formulation, which was enhanced by the administration of very low-dose radiation, could get more of the drug to the brain and less to the bone, thereby make the risk-benefit profile more favorable. […] We show that we can more successfully deliver lower doses of the drug in a more effective manner to the specific sites of tumor within the brain, while sparing the bone toxicity that is seen in younger patients. […] SHH medulloblastoma accounts for around 25% of cases; clinical trials suggest that vismodegib may help some patients, although on-target bone toxicities are a problem. […] By pairing vismodegib with a nanoparticle that targets P-selectin, a transmembrane protein expressed on epithelial cells, Raju and his collaborators enhanced mouse survival without causing the bone toxicity that is normally associated with the SHH pathway inhibitor.

• #91 Neurobiology and Brain Tumor Program | St. Jude Research

  https://www.stjude.org/research/comprehensive-cancer-center/research/neurobiology-and-brain-tumor-program.html

  The integration of histopathologic and molecular features for diagnosis allowed for this paradigm shifting advance that stands to improve treatment stratification for this vulnerable patient population. […] The data collected from NBTP-led studies is used to establish new clinical trials that advance therapy, improve survival and lower morbidity in children with CNS tumors. […] As survival improves, the NBTP focuses on decreasing morbidity and improving quality of life by better understanding the cause of toxicity-related injury and deploying innovative interventions to mitigate these risks.

• #92 Neurobiology and Brain Tumor Program | St. Jude Research

  https://www.stjude.org/research/comprehensive-cancer-center/research/neurobiology-and-brain-tumor-program.html

  The integration of histopathologic and molecular features for diagnosis allowed for this paradigm shifting advance that stands to improve treatment stratification for this vulnerable patient population. […] The data collected from NBTP-led studies is used to establish new clinical trials that advance therapy, improve survival and lower morbidity in children with CNS tumors. […] As survival improves, the NBTP focuses on decreasing morbidity and improving quality of life by better understanding the cause of toxicity-related injury and deploying innovative interventions to mitigate these risks.

• #93 Neurobiology and Brain Tumor Program | St. Jude Research

  https://www.stjude.org/research/comprehensive-cancer-center/research/neurobiology-and-brain-tumor-program.html

  The integration of histopathologic and molecular features for diagnosis allowed for this paradigm shifting advance that stands to improve treatment stratification for this vulnerable patient population. […] The data collected from NBTP-led studies is used to establish new clinical trials that advance therapy, improve survival and lower morbidity in children with CNS tumors. […] As survival improves, the NBTP focuses on decreasing morbidity and improving quality of life by better understanding the cause of toxicity-related injury and deploying innovative interventions to mitigate these risks.

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