Materiały źródłowe

• #1 The molecular pathogenesis of head and neck cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3138532/

  Head and neck cancer arises from a series of molecular alterations progressive from dysplasia to carcinoma in situ, and finally invasive carcinoma. […] The accumulation of these alterations facilitates tumor development. Additionally, the tumor microenvironment enables tumor progression. […] The cooperative effect of molecular alterations in the tumor cells and compensatory microenvironment changes enable tumors to invade and metastasize. […] This review will describe the pathogenesis of head and neck cancer with an emphasis on the genetic and molecular alterations that characterize HNSCC cells and surrounding stroma in the tumor microenvironment. […] The pathogenesis of head and neck cancer is considered a multistep process with an accumulation of genetic mutations, altered protein expression, leading to the development of a unique microenvironment designed to support tumor growth.

• #2 Throat cancer – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/throat-cancer/symptoms-causes/syc-20366462

  Throat cancer refers cancer that develops in your throat (pharynx) or voice box (larynx). […] Throat cancer occurs when cells in your throat develop genetic mutations. These mutations cause cells to grow uncontrollably and continue living after healthy cells would normally die. The accumulating cells can form a tumor in your throat. […] It’s not clear what causes the mutation that causes throat cancer. But doctors have identified factors that may increase your risk.

• #3 Head & Neck Cancers | OncologyPRO

  https://oncologypro.esmo.org/education-library/esmo-books/essentials-for-clinicians/head-neck-cancers/pathogenesis

  Transformation of normal mucosa into invasive HNSCC follows a molecular progression model of multistep carcinogenesis. […] Loss of genetic material from chromosome region 9p21 and inactivation of p16 tumour suppression gene are the earliest alterations identified at transition to hyperplastic mucosa. […] Subsequent transition to dysplasia is characterised by loss of 3p and 17p and by p53 inactivation. Loss of 11q, 13q and 14q precedes transition to carcinoma in situ. […] Loss of 6p, 8p and 4q is identified during transformation to invasive HNSCC. Tobacco-related HNSCC is associated with mutation of p53 and downregulation of p16 protein. […] Leukoplakia and erythroplakia are the precursors of invasive HNSCC in the oral mucosa. […] Field carcinogenesis refers to carcinogen distribution over large areas in upper aerodigestive tracts, due to continuous exposure, rendering mucosa a potential site for cancer.

• #4

  https://www.jci.org/articles/view/59889

  This work, together with a large body of previous genomic and functional analyses of HNSCC, highlights the relatively small number of oncogenes targeted by activating mutations and supports the fundamental roles of tumor suppressor pathways including p53, Rb/INK4/ARF, and Notch in disease pathogenesis. […] The essential role of the retinoblastoma (Rb) pathway is evidenced by the finding of inactivation of CDKN2A, encoding the cell cycle regulators p16/INK4A and p14/Arf/INK4B, in HNSCC. […] The finding that TP53 is mutated in both leukoplakia (a histologically recognizable precursor lesion) and benign-appearing mucosa has led to a patch-field progression model of HNSCC development, in which the index squamous carcinoma (as well as subsequent tumors) develops from a field of genetically abnormal mucosa, itself the result of expansion of a clonal patch arising from a putative stem cell containing a mutated TP53 gene.

• #5 Pathogenesis and Progression of Squamous Cell Carcinoma of the Head and Neck | Oncohema Key

  https://oncohemakey.com/pathogenesis-and-progression-of-squamous-cell-carcinoma-of-the-head-and-neck/

  Clonal evolution theory, proposed by Peter Nowell in 1976, likens cancer to an evolutionary process involving clonal proliferation, genetic diversification, and subclonal selection. […] The cumulative loss of tumor suppressor genes or activation of oncogenes leads to changes in cellular behavior, which confers a survival or proliferative advantage over other cells, ultimately resulting in territorial expansion. […] Eventually, the further accumulation of defects can confer new traits such as immortality, angiogenesis, or the ability to invade. […] These observations led to the field cancerization hypothesis that an entire field of mucosa, which is exposed to the same environmental factors, is at risk for carcinogenesis. […] The cells that possess the necessary characteristics of self-renewal and differentiation have been termed cancer stem cells.

• #6 Pathogenetic Action of Viruses in Head and Neck Cancer | IntechOpen

  https://www.intechopen.com/chapters/1200317

  The tumor suppressor gene TP53 is located on chromosome 17p13 and encodes the nuclear protein p53 (transcription factor), which is involved in maintaining the integrity of the genome and is responsible for the smooth functioning of repair mechanisms in case of DNA damage. […] The ability to understand mutation in relation to viral infection provides an additional physiological dimension to the evolution of viral replication and the strategy by which one can examine mutation. […] Oncogenic viruses contribute to carcinogenesis by altering host epigenomes and using host epigenetic machinery. […] The impacts of virally mediated epigenetic changes on cancer pathology are: (1) epithelial-to-mesenchymal transition, (2) escape from apoptosis, (3) altered cellular metabolism, (4) angiogenesis, (5) inflammation and (6) generation of genomic instability.

• #7 Molecular landscape of head and neck cancer and implications for therapy

  https://atm.amegroups.org/article/view/60770/html

  HNSCC harbor high levels of somatic mutations. They display loss at 3p and 18q and gain at 3q and 8q, with mutations in CDKN2A, TP53, CCND1, EGFR, PIK3CA, PTEN, NOTCH1, NSD1, FAT1, AJUBA and KMT2D. […] Inactivation of p53 protein, encoded by TP53 on 17p12, plays a vital role in the pathogenesis of HNSCC. […] HPV-positive tumours lack mutations and alterations in TP53 and CDKN2A in contrast with their HPV-negative counterparts. […] The p53 and RB pathways are frequently abrogated in HPV-negative HNSCC, but appear to remain active in CNA-silent tumours, with mutations in HRAS and CASP8. […] Smoking is a key etiological risk factor for HPV-negative CNA-high tumours, with many cancer genes (FAT1, NOTCH1) and pathways (WNT–catenin) being involved in their progression.

• #8 The Molecular Pathogenesis of Head and Neck Cancer | Oncohema Key

  https://oncohemakey.com/the-molecular-pathogenesis-of-head-and-neck-cancer/

  Loss of TP53 and CDKN2A, either through mutation or expression of the HPV E6 and E7 proteins, along with amplification of CCND1 favors survival and permits proliferation through the increased activity of cyclin-dependent kinases and loss of p53-dependent apoptosis. […] Inactive, phosphorylated RB pocket proteins are unable to block the G1-to-S phase transition in the setting of p16INK4A loss. […] The mechanism of p16INK4A loss has been shown to be of prognostic value in oral SCC: epigenetic silencing was found to be associated with higher recurrence rates, and deletion with increased rates of nodal metastases. […] The activity of telomerase is detectable by immunostaining in approximately 80% of HNSCC cases analyzed. […] The PI3K-AKT axis is of consequence therapeutically in HNSCC as well, with numerous targeted inhibitors now in clinical trials.

• #9

  https://www.jci.org/articles/view/59889

  The PI3K signaling pathway is commonly activated in HNSCC, as evidenced by recurrent alterations of two central regulators: PTEN, encoding a negative regulator, and PIK3CA, encoding a positive regulator of this pathway. […] New insight into potential mechanisms of HNSCC invasion and metastasis was provided by the identification of mutations in the FAT1 gene in nine HNSCC samples (12%) in one of the two exome sequencing studies.

• #10 Laryngeal cancer pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Laryngeal_cancer_pathophysiology

  Laryngeal cancer arises from squamous cells, which are cells that are normally involved in protection of upper respiratory airway. Genes involved in the pathogenesis of laryngeal cancer include p16, NOTCH1, cyclin D1, and TP53. […] Development of laryngeal cancer is the result of multiple genetic mutations. These mutations lead to activation of oncogenes and inactivation of tumor suppression genes which ultimately result in deregulated cellular proliferation. Genes involved in the pathogenesis of laryngeal cancer include: […] On gross pathology, laryngeal cancer is characterized by: Flattened plaques, Raised margins of the lesion, Mucosal ulceration. […] On microscopic histopathological analysis, laryngeal carcinoma is characterized by: Spindle cells, Basaloid cells, Nuclear atypia, Abundant chromatin.

• #11 The Molecular Pathogenesis of Head and Neck Cancer | Oncohema Key

  https://oncohemakey.com/the-molecular-pathogenesis-of-head-and-neck-cancer/

  The RAS-MAPK and PI3K-ATK pathways interact directly and indirectly, through multiple intermediates. […] In HNSCC, EGFR expression levels are nearly ubiquitously elevated in tumor and tumor-adjacent tissue compared to corresponding normal mucosa. […] Higher expression levels and copy number gain correlate with decreased survival but have not been highly indicative of improved response to EGFR-directed therapy. […] CASP8, a proteolyase responsible for initiating the caspase cascade that drives apoptosis, was found to be mutated in 8% of HNSCC by exome sequencing. […] TP63 expression is present as a gradient. […] In dysplastic mucosa, this patterning is lost, and TP63 expression is evident throughout all layers of the epithelium. […] The exact role of NOTCH signaling in HNSCC remains to be elucidated and is likely tissue and/or context dependent. […] The TGF pathway has been identified as a key player in the EMT process.

• #12 Mechanisms of Invasion in Head and Neck Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469951/

  The best characterized receptor for stimulation of HNSCC invasion is the epidermal growth factor receptor (EGFR). […] Other EGFR ligands besides EGF have been shown to stimulate invasion, including transforming growth factor alpha (TGFA), betacellulin (BTC), heparin binding EGF-like growth factor (HBEGF) and amphiregulin (AREG). […] Inhibition of the EGFR has been shown to block invasion in response to EGF. […] Several signaling pathways have been shown to be important for invasion of HNSCC. […] Inhibition of ERK results in reduced invasion. […] A key distinction between migration and invasion is the ability to degrade extracellular matrix barriers in the latter activity. […] Thus expression of proteases, especially matrix metalloproteases (MMPs), has been shown to be important for HNSCC invasion in a number of cases.

• #13 Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01503-1

  c-MET is overexpressed in 78% of HNSCC cases having phosphorylated at active sites Y1230, Y1234 and Y1235. Aberrant c-MET signaling promotes tumor progression and enables the development of distant metastasis by increasing the invasive capacity of HNSCC tumor cells. This signaling pathway also stimulates the morphogenesis of epithelial cells to acquire this aggressive metastatic phenotype via epithelial-mesenchymal transition (EMT). […] Increased expression of c-MET signaling takes place due to variety of genetic abnormalities including MET mutations and amplification of the MET gene. MET mutations are frequently observed in the MET tyrosine kinase domain, sema and juxtamembrane domains in HNSCC patient tumors. […] The c-MET/HGF signaling is also known to contribute widely in metabolic reprogramming of tumor cells. Increased glucose metabolism is highly preferred by cancer cells to yield much higher ATP and it also generates biosynthesis relevant precursor molecules.

• #14 Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01503-1

  An aberrant HGF/c-MET signaling can lead to uncontrolled proliferation, motility, invasiveness, and angiogenesis and can play an essential role in the development, progression and survival of cancer including head and neck squamous cell carcinoma (HNSCC). […] HGF activates c-MET receptor in a paracrine manner by exerting its pleotropic effects through controlling several transmission cascades such as the mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 kinase (PI3K)/AKT, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. […] Activation of HGF/c-MET signaling requires phosphorylation of several elements in the c-MET receptor. Once HGF binds to the c-MET receptor autophosphosphorylation of several tyrosine residues takes place in the intracellular region. The activation of intracellular kinase activity of c-MET takes place via phosphorylation of Y1230, Y1234 and Y1235.

• #15 Throat Cancer: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/23136-throat-cancer

  Throat cancer happens when something triggers genetic mutations (changes) in the cells in your throat. The mutation turns healthy cells into cancerous cells that grow and multiply. Without treatment, they can spread to other parts of your body. Researchers are investigating what triggers these changes. […] Factors that increase your chance of developing throat cancer include: […] Tobacco use is the single largest risk factor for developing throat cancer. […] HPV infection is now the most common cause of new throat cancer cases. […] Cancer staging allows healthcare providers to determine how advanced throat cancer is. Its an important part of your diagnosis. […] Healthcare providers use different therapies to treat throat cancer. […] Targeted therapy blocks proteins cancer cells use to grow. Immunotherapy helps activate your immune system to fight cancer. […] Your outcome (prognosis) depends on lots of factors unique to you. Healthcare providers can sometimes cure throat cancer that hasnt spread to nearby tissues or lymph nodes. But more advanced cancers are harder to treat. Theyre more likely to come back after treatment.

• #16 Throat Cancer | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/cancer-care/types/throat

  Throat cancer is a form of head and neck cancer. It usually starts in the throat (pharynx), the voice box (larynx), the vocal cords, or the tonsils. […] Like mouth cancer, cancer of the throat is often associated with tobacco and alcohol use. But in recent years, infection with the human papillomavirus (HPV) has emerged as a major cause of tonsil cancer and other cancers of the oropharynx. In fact, according to the Centers for Disease Control, more than 70 percent of the oropharyngeal cancer diagnosed in the United States is linked to HPV. […] Throat cancer treatments may include head and neck surgery, radiation therapy, drug therapy, or a combination of these. Which approach is right for you depends on many factors. These include the size and location of the tumor, whether the tumor is linked to HPV infection, and your own personal preferences.

• #17 Head & Neck Cancers | OncologyPRO

  https://oncologypro.esmo.org/education-library/esmo-books/essentials-for-clinicians/head-neck-cancers/pathogenesis

  HPV infection carcinogenesis: The integration of HPV DNA into the host genome disrupts the expression of factor E2, the transcriptional repressor of E6 and E7 viral proteins. […] E6 and E7 encode oncoproteins that bind and degrade p53 and retinoblastoma (Rb) tumour suppressors, respectively. Degradation of Rb induces expression of p16INK4A. […] Rb is a negative regulator of p16 protein; low Rb levels lead to p16 upregulation. HPV+ OPC is typically p53 and Rb1 wild-type and demonstrates high p16 protein levels.

• #18 Pathogenetic Action of Viruses in Head and Neck Cancer | IntechOpen

  https://www.intechopen.com/chapters/1200317

  By interfering with the regulation of the cell cycle, evading immune monitoring and encouraging genomic instability, these viruses thwart cell transformation. […] The early oncogenes E6 and E7, for instance, are overexpressed when HPV DNA is incorporated into host cells, inactivating the tumor suppressor proteins p53 and Rb, respectively. […] About 70% of oropharyngeal malignancies (OPCs) in the US are caused by HPV, and the incidence of HPV-associated HNCs, particularly oropharyngeal squamous cell carcinoma (OPSCC), is rising sharply. […] In the same way, EBV is involved in almost all nasopharyngeal cancers and a considerable percentage of head and neck lymphomas, exhibiting complicated viral interactions in the tumor microenvironment. […] Understanding how oncogenic viruses and host factors interact is essential for creating tailored treatment plans that effectively stop the progression of HNC while lowering treatment-associated morbidity.

• #19 Pathogenetic Action of Viruses in Head and Neck Cancer | IntechOpen

  https://www.intechopen.com/chapters/1200317

  EBV is classified as a Group I carcinogen by IARC. […] EBV adopts a hit and run tactic, manipulating host epigenetic procedures to start an oncogenic pathway even after the virus has been eliminated. […] Latent viral proteins, including EBV nuclear antigen (EBNA) and latent membrane proteins (LMPs), which disrupt cell function, promote proliferation and halt apoptosis, are responsible for the carcinogenic consequences of EBV. […] HHV-8 exerts its oncogenic effects through viral proteins that establish latent infection in endothelial cells, disrupt cellular control mechanisms and promote uncontrolled cell proliferation and survival. […] The ongoing investigation of these viruses in head and neck cancers (HNCs) shows potential for enhancing diagnostic, preventive and therapeutic strategies, which could ultimately lead to improved patient outcomes and quality of life.

• #20 Pathogenetic Action of Viruses in Head and Neck Cancer | IntechOpen

  https://www.intechopen.com/chapters/1200317

  Head and neck cancer (HNC) represents a heterogeneous group of neoplasms with different biological and clinical behavior, which develops in the upper parts of the respiratory and digestive tract outside the esophagus. […] Oncogenic viruses play an important role in the development of HNC. Human papillomavirus (HPV) has been extensively studied in relation to oropharyngeal carcinoma, but other oncogenic viruses also contribute to the HNC onset. […] Among the multifaceted factors in the development of HNC, oncogenic viruses have appeared as an important factor profoundly influencing both the starting and progression of these malignant tumors. […] Seven human carcinogenic viruses are currently known as viruses with potential oncogenic dynamic in the head and neck region, including five DNA viruses: hepatitis B virus (HBV), Kaposi’s sarcoma herpes virus or human herpes virus 8 (KSHV or HHV-8), Merkel cell polyomavirus (MCPV), Epstein-Barr virus (EBV) and human papillomavirus (HPV).

• #21 Pathogenetic Action of Viruses in Head and Neck Cancer | IntechOpen

  https://www.intechopen.com/chapters/1200317

  The identification and characterization of viral involvement in HNC has been transformed by advancements in detection techniques, including next-generation sequencing (NGS), highly sensitive polymerase chain reaction (PCR) assays, and sophisticated imaging. […] The goal is to clarify the various roles that HPV, EBV and other associated viruses play in various HNC subtypes by combining the most recent research on these viruses. […] The mechanisms by which oncogenic viruses induce oncogenic transformation vary, but all have important common features. […] Studies of the oncogenic activity of proteins encoded by oncogenic viruses, especially DNA viruses, have greatly contributed to elucidating the role of retinoblastoma (Rb) proteins and the repressor gene p53 as regulators of cell growth.

• #22 Mechanisms of Invasion in Head and Neck Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469951/

  The highly invasive properties demonstrated by Head and Neck Squamous Cell Carcinoma (HNSCC) is often associated with locoregional recurrence and lymph node metastasis in patients, and is a key factor leading to an expected 5-year survival rate of approximately 50% for patients with advanced disease. […] It is important to understand the features and mediators of HNSCC invasion so that new treatment approaches can be developed. […] Cell surface receptors, signaling pathways, proteases, invadopodia function, epithelial-mesenchymal transition, microRNAs, and tumor microenvironment are all involved in the regulation of the invasive behavior of HNSCC cells. […] Identifying effective HNSCC invasion inhibitors has the potential to improve outcomes for patients by reducing the rate of spread and increasing responsiveness to chemoradiation.

• #23 Mechanisms of Invasion in Head and Neck Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469951/

  The ability of tumors to invade into surrounding tissues is a hallmark of cancer and is arguably the property that most greatly impacts morbidity and mortality. […] This property is achieved during the process of carcinogenesis as multiple genetic insults are accumulated and in turn the acquisition of invasive capabilities allows invasion through the basement membrane. […] Depth of invasion (DOI) for these tumors is directly associated with patient outcome, and as the depth approaches 24 mm of invasion, the rate of lymph node metastasis increases greatly and prognosis worsens. […] Therefore, elective neck dissection is recommended for oral tongue cancers with a depth of invasion of more than 24 mm, even when no clinical evidence of lymph node spread exists. […] The invasive front of an invading tumor has been shown to be an important indicator of patient prognosis.

• #24 Mechanisms of Invasion in Head and Neck Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469951/

  The most commonly identified MMP has been MMP9. […] MMP9 can degrade type IV collagen, a key constituent of the basement membrane, and thus has the potential to play an important role in enabling HNSCC cells to become frankly invasive. […] Cell-cell adhesion mediated by E-cadherin is generally found to inhibit invasion. […] Induction of cell-cell junctions can inhibit invasion. […] Epithelial to mesenchymal transition (EMT) is a highly regulated process in which epithelial cells acquire a mesenchymal morphology through coordinated changes in gene and protein expression that lead to decreased cell adhesion and cell polarity, resulting in a more invasive phenotype. […] HNSCC cells that undergo EMT have been shown to be more invasive. […] The loss of E-cadherin associated with EMT has shown to be an indicator of poor prognosis in HNSCC.

• #25 Pathogenesis and Progression of Squamous Cell Carcinoma of the Head and Neck | Oncohema Key

  https://oncohemakey.com/pathogenesis-and-progression-of-squamous-cell-carcinoma-of-the-head-and-neck/

  The clonal evolution theory suggests that many alterations are needed for cells to gradually transform into cancer. […] The quintessential tumor suppressor p53 plays a central role in guarding the genome by activating DNA repair, cell cycle arrest, or apoptosis in response to genetic damage or cellular stresses. […] Dysregulation of Proliferative Signaling Cells within normal tissues have a tightly regulated balance of proliferative and antiproliferative signaling that govern cellular growth and replication, thus ensuring homeostasis between cell population and host resources. […] In cancer cells, cell cycle checkpoints are universally circumvented to allow for aberrant cellular proliferation. […] The tumor suppressors Rb and p53 help to suppress proliferative activity as well. […] The nearly ubiquitous, though heterogeneous, insults to the gatekeeper circuits indicate that this is one of the key requirements for development or progression of HNSCC. […] The process of EMT is mediated by four major transcription factors: Snail, Slug, Twist, and Zeb 1/2. […] These changes are needed for the destructive invasive properties of HNSCC as well as for processes associated with lymphatic and hematogenous metastases.

• #26 Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01503-1

  The tumor microenvironment (TME) is a complex tissue structure composed of fibroblasts, blood vessels, immune cells and the extracellular matrix. The TME surrounded through the cancer cells help in the development, progression, drug resistance and metastasis. […] Chemoresistance has been a topic of concern ever since cancer cells have found their own ways to escape the inhibitory effects of chemodrugs. In a similar concern, therapies targeting EGFR has found resistance to the treatment due to the activation of c-MET signaling axis. […] c-MET has a major contribution towards compensating for inhibition of RTK pathways that help in proliferation and metastasis in HNSCC. Therefore, targeting c-MET along with other receptor tyrosine kinases can bring effective therapeutic strategies.

• #27 Mechanisms of Invasion in Head and Neck Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7469951/

  Cancer associated fibroblasts (CAFs) are the major stromal cells present in the microenvironment of HNSCC, and these tend to be myofibroblasts showing increased expression of alpha-smooth muscle actin. […] Myofibroblasts and CAFs have been shown to enhance HNSCC invasion in vitro in a variety of assays. […] The mechanism of stimulation of tumor cell invasion by CAFs can include induction of EMT. […] Hypoxia in the tumor microenvironment can induce Notch and EMT factors, such as Slug and Snail, to increase invasion. […] DNA changes such as mutations and copy number variations (CNVs) at the genomic level have been implicated in cancer progression. […] Higher numbers of CNVs in the genome are associated with the development of cancer, and more CNVs are accumulated with tumor progression.

• #28

  https://journals.lww.com/indianjcancer/fulltext/2006/43020/oral_squamous_cell_carcinoma__etiology,.2.aspx

  The TSG p53, is called as Guardian of the Genome, having a role in maintaining genomic stability, cell cycle progression, cellular differentiation, DNA repair and apoptosis. […] The deregulation of apoptosis-related genes, aids in successful carcinogenesis. […] These studies thus indicate, that evasion of apoptosis via abnormal expression of bcl-2, bclxL, mcl-1 and p53, may contribute to oral cancer pathogenesis. […] The ribonucleoprotein enzyme telomerase extends the telomeric repeat sequences at the chromosomal ends; and it is active in a majority (90%) of human neoplasia, but inactive in most normal cells. […] High telomerase activity in oral tumors and in 37% of OSCC patients, using oral rinses. […] Angiogenesis, defined as the growth of new blood vessels (neovascularization) from pre-existing ones, is a complex process, absolutely needed for the continued growth and survival of solid neoplasia. […] The steps critical to successful angiogenesis, include the degradation of the extracellular matrix, endothelial cell proliferation, migration and assembly of endothelial cells into higher order structures.

• #29 The Molecular Mechanisms of Tobacco in Cancer Pathogenesis

  https://brieflands.com/articles/ijcm-7902

  Apoptosis or programmed cell death takes part in controlling cell growth, homeostasis, and removal of abnormal cells. Defects in apoptosis pathway lead to cell survival and unlimited cell growth. In most cancers, resistance to apoptosis is observed mostly due to gene mutations. […] Angiogenesis, the formation of new blood vessels from endothelial cells, is a critical event for nutrition and oxygen delivery to tumor cells. Tumor cells stimulate angiogenesis by up-regulating the expression of different growth factors, such as VEGF and bFGF. […] The process of tumor metastasis, which is the principle cause of mortality among cancer patients, is the spread of tumor cells from one organ or part of the body to other parts. Clinical and epidemiological studies have shown that progression and metastasis of cancer in smokers is faster than others.

• #30 Local hyperthermia in head and neck cancer: mechanism, application and advance | Oncotarget

  https://www.oncotarget.com/article/10350/text/

  Local HT could contribute to changing tumor vessel perfusion and pO2, through activating HIF-1 and its downstream targets, such as VEGF and pyruvate dehydrogenase kinase 1(PDK1), and modifying tumor cell metabolism signaling pathways. […] The acquisition of thermotolerance in cancer cells renders hyperthermia less effective. […] Heat-stressed tumor cells release heat-shock proteins (HSPs), including HSP27, HSP70, HSP90, which can bind to and activate antigen-presenting cells (APCs) in the next step. […] A great deal of attention has been focused on the ability and molecular mechanism of HT to regulate the anti-tumor immunity system. […] Tumor-cell derived exosomes are recognized as potential immunostimulatory factors, due to containing large amounts of tumor antigens. […] Local hyperthermia, a common heat therapy, is specially suitable for head and neck cancers because of their superficial anatomic sites.

• #31 Scientists uncover a mechanism that could lead to new immunotherapies head and neck cancer

  https://medicalxpress.com/news/2020-03-scientists-uncover-mechanism-immunotherapies-neck.html

  Researchers at UC have discovered a previously unknown mechanism that could explain the reason behind decreased immune function in cancer patients and could be a new therapeutic target for immunotherapy for those with head and neck cancers. […] Led by Laura Conforti, professor in the Department of Nephrology and Hypertension at the UC College of Medicine, the team discovered that a reduced interaction between a molecule called calmodulin and an ion channel (KCa3.1) in the immune cells of cancer patients plays an important role in the reduced function of these cells. […] „Identifying the mechanism of this underlying dysfunction can help us identify molecules that we can target with drugs and ultimately restore the ability of these cells to enter and kill the tumors,” says Conforti. […] „In this study, we were able to show that the function of these channels in T-cells from cancer patients is decreased which results in a decreased T-cell accumulation in solid tumors,” Conforti says.

• #32 Scientists uncover a mechanism that could lead to new immunotherapies head and neck cancer

  https://medicalxpress.com/news/2020-03-scientists-uncover-mechanism-immunotherapies-neck.html

  „As previously stated, the channels do not function if the calmodulin does not bind to them. Thus, the decreased calmodulin binding in T-cells from cancer patients results in decreased function and leads to reduced tumor infiltration and killing of the cancer cells.” […] „These findings strengthen the therapeutic potentials of [these] activators, which could restore cytotoxic T-cell functionality and can ultimately lead to additional immunotherapeutic options for patients with cancer,” Conforti adds.

• #33 Updates on Larynx Cancer: Risk Factors and Oncogenesis

  https://www.mdpi.com/1422-0067/24/16/12913

  Laryngeal cancer is a very common tumor in the upper aero-digestive tract. Understanding its biological mechanisms has garnered significant interest in recent years. The development of laryngeal squamous cell carcinoma (LSCC) follows a multistep process starting from precursor lesions in the epithelium. […] Cancer development involves multiple steps, and genetic alterations play a crucial role. Tumor suppressor genes can be inactivated, and proto-oncogenes may become activated through mechanisms like deletions, point mutations, promoter methylation, and gene amplification. […] According to the latest evidence, epigenetic modifications have been proven to contribute to LSCC development. Particularly, lncRNAs, miRNAs, and mRNAs play a relevant role in cancer development, including differentiation, proliferation, and apoptosis of cancer cells.

• #34 Pathogenesis and Progression of Squamous Cell Carcinoma of the Head and Neck | Oncohema Key

  https://oncohemakey.com/pathogenesis-and-progression-of-squamous-cell-carcinoma-of-the-head-and-neck/

  High-risk HPV is now causatively linked to the majority of oropharyngeal squamous cell carcinomas (OPSCCs). […] The CDKN2A gene encodes a protein (p16INK4a) important in cell cycle regulation, as detailed later. […] Overall, due to the rarity of these predisposing syndromes and germline mutations, patients with HNSCC with these syndromes constitute a very small percentage of all HNSCC. […] The most well-characterized epigenetic alterations are DNA methylation and histone modifications. […] In HNSCC, promoter methylation of genes such as CDKN2A (encoding p16INK4a and p14ARF), DAPK, RASSF1A, RARB2, APC, and MGMT is often an early event during neoplastic progression. […] The characteristic phenotypic changes, or hallmarks, seen in cancer cells have been frequently described and updated in recent years.

• #35 The Molecular Mechanisms of Tobacco in Cancer Pathogenesis

  https://brieflands.com/articles/ijcm-7902.html

  Studies have shown that cancer is a multi-factorial disease in its pathogenesis, in addition to genetic disorders, the effect of environmental factors can also be pointed. Among all environmental factors, tobacco that is considered as the leading cause of respiratory and cardiovascular disease plays a key role in cancer pathogenesis and progression. More than 5,000 chemicals and 62 carcinogenes have been detected in tobacco, which could contribute to tumorgenesis through activating oncogenes, inhibition of tumor suppressor genes, genetic and epigenetic changes, alteration of growth pathways, angiogenesis and metastasis. […] This review explains the association between tobacco smoking and the incidence of different human cancers; also it focuses on molecular mechanisms through which carcinogenic chemicals in tobacco smoke promote cancer progression. Among multiple components of tobacco smoke, three carcinogens, including polycyclic aromatic hydrocarbons (PAH), nictotine and nicotin-derived nitrosamine ketone (NNK) convincingly play major roles in the pathogenesis of a wide range of cancers. In fact, these toxic and carcinogenic agents alter the expression of oncogenes, tumor suppressors, DNA repair, and last but not least, apoptosis-related genes through several mechanisms, such as point mutations, deletions, translocations and gene recombination. Moreover, implication of different tumorgenic signal transduction pathways, such as PI3K/AKT, STAT3, ERK1/2 and COX-2 in tobacco-induced tumorgenesis should not be underestimated.

• #36 Head and neck cancer | World Cancer Research Fund

  https://www.wcrf.org/preventing-cancer/cancer-types/head-and-neck-cancer/

  Head and neck cancers are caused by damaged cells, which can grow uncontrollably to form a tumour. […] Evidence for what causes head and neck cancer comes from large population studies (called epidemiology) and biological studies (where scientists look at cells in a laboratory). […] Smoking (or the use of smokeless tobacco, sometimes called chewing tobacco or snuff) increases the risk of head and neck cancers. […] Drinking alcohol increases the risk of head and neck cancer. […] As much as 90 per cent of mouth cancers worldwide are attributable to tobacco, alcohol or a combination of the 2 together. […] Infection with human papilloma virus (HPV) increases the risk of head and neck cancer. […] Our Expert Panel of scientists has also looked at other things that may be linked with the risk of head and neck cancer. […] For scientists: full references, pathogenesis and a summary of the mechanisms underpinning our findings on how to prevent head and neck cancer can be found in our 2018 mouth, pharynx and larynx cancer report.

• #37 Pathology Outlines – Squamous cell carcinoma of larynx

  https://www.pathologyoutlines.com/topic/larynxscc.html

  Combined smoking and alcohol use have a multiplicative effect on risk […] HPV is found in a minority of cases, with recent studies finding 11.6% and 13% of cases positive (J Pathol Transl Med 2020;54:411, Oral Oncol 2019;98:20) […] Unlike oropharyngeal SCC, the role of HPV in the carcinogenesis of laryngeal SCC has not been established (Head Neck 2011;33:581, Nat Rev Dis Primers 2020;6:92)

• #38 Local hyperthermia in head and neck cancer: mechanism, application and advance | Oncotarget

  https://www.oncotarget.com/article/10350/text/

  Local hyperthermia (HT), particularly in conjunction with surgery, radiotherapy and chemotherapy was useful for the treatment of human malignant tumors including head and neck cancer. […] The mechanism of local HT mainly includes the following aspects: […] To individual cancer cells, heating could change cell membrane permeability and receptors, alter enzyme activity and cellular structure, to induce cell apoptosis. […] Exposure of cells to heating causes a rapid translocation of nucleolin from the nucleolus into the nucleoplasm, which inhibits DNA replication and synthesis. […] Heating after irradiating significantly can reduce the dose of radiation therapy. […] HT is a potent radiation sensitizer. […] Moderate HT leads to increased vascular permeability and increase in oxygen pressure levels in the tumors.

• #39 Throat Cancer | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/cancer-care/types/throat

  Knowing the HPV status of a throat tumor is very important. Many times people with HPV-positive throat cancer can receive less-intensive treatment. MSKs throat cancer specialists are pioneering new treatment approaches that can lead to better long-term outcomes. […] People with advanced throat cancer may benefit from cutting-edge therapies, such as immunotherapy or targeted therapy. These are often offered through clinical trials. MSK runs one of the largest head and neck cancer clinical trial programs in the United States.

• #40 Role of Glutathione in Head and Neck Cancer Pathogenesis: Khan, Sami Ullah: 9786202511957: Amazon.com: Books

  https://www.amazon.com/Role-Glutathione-Head-Cancer-Pathogenesis/dp/6202511958

  These changes in glutathione levels in blood and tumors of head and cancer may be due to increased utilization of glutathione due to variant genotypes and reactive oxygen species (ROS). […] We concluded that the glutathione levels in head and neck cancer patient’s blood or tissues may act as a prognostic marker of head and neck cancer, thus deserves further investigations.

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