Materiały źródłowe

• #1 Stem-like Cells Proteome Holds Clues to Pathogenesis of Oral Cancer?

  https://www.thermofisher.com/blog/proteomics/does-the-stem-like-cell-proteome-hold-clues-to-the-pathogenesis-of-oral-cancer/

  Oral squamous cell carcinoma is yet another common cancer with typically late presentation, high recurrence after treatment and a poor five-year survival rate. […] One factor thought to contribute to these dire statistics is the presence of sub-populations of cancer stem-like cells (CSCs) within a tumor. These cells are thought to be involved in tumor initiation and growth, metastatic spread, resistance to chemotherapy and tissue invasion. […] The authors suggest that differential levels of protein expression in their proteome (as compared with the non-CSC UM1 cells) could explain the malignant phenotype commonly seen with other CSCs. […] Misuno et al. are confident that their results show potential for further investigation of oral cancer pathogenesis and offer clues for developing therapeutic interventions.

• #2 Nerves in Oral Cancer: Mechanism of Interaction and Clinical Relevance

  https://deepblue.lib.umich.edu/handle/2027.42/174397

  Patients with oral squamous cell carcinoma, the most common oral cancer, survive poorly. […] Importantly, these criteria do not integrate the biology of cancer-nerve interactions. […] To address these knowledge gaps, we investigated the clinical significance of PNI and other neural phenotypes in oral cancer, and investigated the underlying mechanisms. Understanding how these mechanisms contribute to clinical outcomes is crucial for developing new treatment strategies to improve survival of patients with oral cancer. […] Our results from tumor specimens of 142 patients with oral cancer, demonstrate that PNI is an independent predictor of poor prognosis. […] Clinical studies on the neural influence in oral cancer were integrated with mechanistic studies. […] Together these studies show that multiple neural phenotypes including PNI, nerve-tumor distance, nerve diameter, and nerve density, are of clinical significance in progression of oral cancer.

• #3 Molecular pathogenesis of oral squamous carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1186964/

  Oral squamous carcinogenesis is a multistep process in which multiple genetic events occur that alter the normal functions of oncogenes and tumour suppressor genes. This can result in increased production of growth factors or numbers of cell surface receptors, enhanced intracellular messenger signalling, and/or increased production of transcription factors. In combination with the loss of tumour suppressor activity, this leads to a cell phenotype capable of increased cell proliferation, with loss of cell cohesion, and the ability to infiltrate local tissue and spread to distant sites. […] Oral carcinogenesis is a multistep process in which genetic events lead to the disruption of the normal regulatory pathways that control basic cellular functions including cell division, differentiation, and cell death. Several studies have shown that there is a genetic component in the development of carcinoma.

• #4 Tongue Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562324/

  Tongue cancer is one of the most common sites of head and neck malignancy. Smoking, drinking alcohol, and, more recently, human papilloma virus infection are recognized as the major risk factors for the development of tongue cancer. […] The two most important independent risk factors for the development of tongue SCCA are heavy smoking and alcohol use. Cigarette smoke contains known carcinogens, mainly nitrosamines, and polycyclic hydrocarbons. Alcohol metabolizes into acetaldehyde, which affects DNA repair. […] A fundamental, albeit simplified concept in oncogenesis, is the overexpression of oncogenes and silencing of tumor suppressor genes. Environmental lifetime exposure of the oral cavity to known carcinogenic agents leads to DNA damage, and the accumulation of genetic events ultimately leads to the development of carcinoma. Despite numerous genetic alterations that have been linked with the development of cancer, we have only begun to scratch the surface in terms of understanding the relationship between these genetic changes and their relative importance in carcinogenesis. Two of the most well-established genetic alterations that lead to tongue cancer, and head and neck squamous cell carcinoma in general, are mutations in the tumor suppressor gene p53 and overexpression of epidermal growth factor receptor (EGFR) oncogene.

• #5 Molecular pathogenesis of oral squamous carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1186964/

  Whether patients develop single site oral cancer or multiple site oral cancer, much evidence has accumulated to suggest that multiple genetic events lead to oral cancer, with around six to 10 genetic events believed to result in oral carcinogenesis. However, the importance of both the known gene alterations and as yet unidentified oncogenes and tumour suppressor genes is still not fully understood. […] Several studies have identified specific genetic alterations in oral carcinomas and in premalignant lesions of the oral cavity. […] Loss of heterozygosity (LOH) was reported at 9p21p22 in 72% of tumours. […] Allelic loss of 3p and 9p and other regions containing tumour suppressor genes has also been reported in precursor lesions of oral cancer showing varying degrees of dysplasia compared with normal epithelium.

• #6 Tongue cancer pathophysiology – wikidoc

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

  Leukoplakia and erythroplakia have the greatest potential for malignant transformation into tongue cancer. […] Genes involved in the pathogenesis of tongue cancer include TP53, c-myc, and erb-b1. […] Leukoplakia is considered a premalignant condition from the chronic irritation of the mucous membranes, resulting in increased rates of epithelial and connective tissue proliferation. […] Erythroplakia is considered as the earliest sign of asymptomatic cancer by Mashberg. […] The carcinogens in tobacco smoke, for example, increase the prevalence and spectrum of TP53 mutations. […] Local tumor recurrence reflects extension of genetically damaged cells beyond the clinical and microscopic boundaries of carcinoma to the margins of surgical resection. […] Tongue cancer constitutes of highly differentiated squamous cells lacking frank cytologic criteria of malignancy with rare mitoses. […] The surface of the lesion is covered with compressed invaginating folds of keratin layers. A stroma-like inflammatory reaction and a blunt pushing margin may be seen.

• #7 Cancers of the Oral Mucosa: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1075729-overview

  In oral SCC, modern DNA technology, especially allelic imbalance (loss of heterozygosity) studies, have identified chromosomal changes suggestive of the involvement of tumor suppressor genes (TSGs), particularly in chromosomes 3, 9, 11, and 17. Functional TSGs seem to assist growth control, while their mutation can unbridle these control mechanisms. […] The regions most commonly identified thus far have included some on the short arm of chromosome 3, a TSG termed P16 on chromosome 9, and the TSG termed TP53 on chromosome 17, but multiple other genes are being discovered. […] As well as damage to TSGs, cancer may also involve damage to other genes involved in growth control, mainly those involved in cell signaling (oncogenes), especially some on chromosome 11 (PRAD1 in particular) and chromosome 17 (Harvey ras [H-ras]). Changes in these and other oncogenes can disrupt cell growth control, ultimately leading to the uncontrolled growth of cancer.

• #8 Tongue cancer overview – wikidoc

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

  Tongue cancer is cancer that begins in the cells of the tongue. […] Genes involved in the pathogenesis of tongue cancer include TP53, c-myc, and erb-b1. […] Leukoplakia and erythroplakia have the greatest potential for malignant transformation in tongue cancer. […] Tongue cancer constitutes of highly differentiated squamous cells lacking frank cytologic criteria of malignancy with rare mitoses. […] Tongue cancer is caused by a point mutation in the tumor suppressor gene (TP53). The other oncogenes associated with oral squamous cell cancers of tongue include c-myc and erb-b1.

• #9 Molecular pathogenesis of oral squamous carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1186964/

  The retinoblastoma tumour suppressor gene regulates the cell cycle by the hypophosphorylated protein pRb preventing cells from transition across the G1 checkpoint, by sequestering transcription factors such as E2F, which activate S phase genes. […] In some reports, lack of pR6 expression has been observed in 66% of oral squamous carcinomas and 64% of premalignant lesions. […] Alteration in pRb/p16 expression correlated with heavy consumption of betel and tobacco, suggesting that alteration in the p16/pR6 pathway is an early event in oral tumorigenesis and might be involved in the development of betel and tobacco related malignancies. […] Our understanding of the molecular basis of oral squamous carcinoma has increased rapidly over the past few years. Multiple genetic events that culminate in carcinogenesis include the activation of oncogenes and inactivation of tumour suppressor genes. However, not all genetic events occur in all squamous oral carcinomas and similar genetic alterations may occur at different times in the process of carcinogenisis.

• #10 Oral squamous cell carcinomas: state of the field and emerging directions | International Journal of Oral Science

  https://www.nature.com/articles/s41368-023-00249-w

  Persistent exposure to these risk factors results in genetic alterations, epigenetic modifications, and a dysregulated tumor microenvironment, all of which contribute to the occurrence and transformation of OPMDs to OSCC. The genetic alterations result in the aberrant activation of oncogenic pathways, such as EGFR, Wnt/-catenin, JAK/STAT, NOTCH, PI3K/AKT/mTOR, MET, and RAS/RAF/MAPK, as well as disruptions of suppressor pathways, such as TP53/RB, p16/Cyclin D1/Rb, which significantly contribute to the progression of OSCC. […] Epigenetic modifications, such as DNA methylation, histone covalent modification, chromatin remodeling, and gene regulation by non-coding RNAs (ncRNAs), participate in OSCC formation and development. […] Overall, Wnt/-catenin signaling has a vital role to play in the formation of oral malignancies.

• #11

  https://pubs.thesciencein.org/journal/index.php/cbl/article/view/a652

  Oral cancer is caused and developed by multiple molecular and cellular pathways such as PI3K/AKT/mTOR, Ras-Raf-MEK-ERK pathway, Wnt signaling, NF-B pathway, Hippo pathway, etc. […] Genetic anomalies, the upregulation of several proteins, the deregulation of tumor-suppressive and oncogenes, and risk factors like alcohol and tobacco consumption are a few examples of the known irregularities that contribute to the development of oral cancer through the accumulation of various carcinogenic substances. […] Therefore, it is crucial to have a deep understanding of these pathways to properly understand the development of oral cancer.

• #12 Revealing molecular mechanisms of early-onset tongue cancer by spatial transcriptomics | Scientific Reports

  https://www.nature.com/articles/s41598-024-76044-2

  Tongue cancer at a young age demonstrates an increase in incidence, aggressiveness, and poor response to therapy. Classic etiological factors for head and neck tumors such as tobacco, alcohol, and human papillomavirus are not related to early-onset tongue cancer. Mechanisms of development and progression of this cancer remain unclear. […] Oxidative stress, vascular mimicry, and MAPK and JAK-STAT pathways were enriched in early-onset tongue cancer. […] Taken together, these results indicate that early-onset tongue cancer has distinct transcriptomic features and molecular mechanisms compared to older patients. […] The mechanisms of early-onset TSCC are unclear due to a lack of complex investigation of tumor and microenvironment cell compartments. […] Unlike older patients, TSCC of young adults was found to be enriched with immunosuppressive gene signature, oxidative stress, the MAPK and JAK-STAT molecular pathways, as well as with plasma cells, TAMs and vascular mimicry features at the invasive front.

• #13 Revealing molecular mechanisms of early-onset tongue cancer by spatial transcriptomics | Scientific Reports

  https://www.nature.com/articles/s41598-024-76044-2

  Early-onset TSCC demonstrates extremely downregulated oxidative phosphorylation and upregulated glycolysis, pentose-phosphate pathway, and glutathione metabolism. […] The key molecular player in early-onset TSCC development is most likely the MAPK signaling pathway, which can be activated by immunosuppressive cells and upregulated in response to hypoxia and oxidative stress. […] In addition, the tumor core of early-onset TSCC was enriched by the interaction of urokinase (PLAU) with integrins v5, which are known to activate ERK1/2, a key component of the MAPK signaling pathway. […] The invasive edge of early-onset TSCC was also found to be enriched with vascular mimicry demonstrating upregulation of the JAK-STAT signaling pathway genes and surrounded by TAMs, which may induce or support this process.

• #14 Molecular pathogenesis of oral squamous carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1186964/

  There has been much research on the tumour suppressor gene p53. The p53 protein blocks cell division at the G1 to S boundary, stimulates DNA repair after DNA damage, and also induces apoptosis. […] Mutation of p53 occurs either as a point mutation, which results in a structurally altered protein that sequesters the wild-type protein, thereby inactivating its suppressor activity, or by deletion, which leads to a reduction or loss of p53 expression and protein function. […] p53 has been shown to be functionally inactivated in oral tumours, and restoration of p53 in oral cancer lines and tumours induced in animal models has been shown to reverse the malignant phenotype. […] In general, tumour suppressor genes are thought to act recessively so that both copies of the gene must be inactivated for malignancy to occur.

• #15 Molecular pathogenesis of oral squamous carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1186964/

  The retinoblastoma tumour suppressor gene regulates the cell cycle by the hypophosphorylated protein pRb preventing cells from transition across the G1 checkpoint, by sequestering transcription factors such as E2F, which activate S phase genes. […] In some reports, lack of pR6 expression has been observed in 66% of oral squamous carcinomas and 64% of premalignant lesions. […] Alteration in pRb/p16 expression correlated with heavy consumption of betel and tobacco, suggesting that alteration in the p16/pR6 pathway is an early event in oral tumorigenesis and might be involved in the development of betel and tobacco related malignancies. […] Our understanding of the molecular basis of oral squamous carcinoma has increased rapidly over the past few years. Multiple genetic events that culminate in carcinogenesis include the activation of oncogenes and inactivation of tumour suppressor genes. However, not all genetic events occur in all squamous oral carcinomas and similar genetic alterations may occur at different times in the process of carcinogenisis.

• #16 Molecular pathogenesis of oral squamous carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1186964/

  The cyclin dependent kinase inhibitor 2/multiple tumour suppressor gene 1 (CDKN2/MTSI) has been mapped to this chromosome region, and inactivation of its protein product p16INK4 by mutation and deletion has been found in 10% and 33% of head and neck squamous carcinomas, respectively, along with frequent inactivation of p16 in oral premalignant lesions. This suggests an important role for this gene in the early stages of oral carcinogenesis. […] Oncogenes are altered growth promoting regulatory genes that govern the cells’ signal transduction pathways, and mutation of these genes leads to either overproduction or increased function of the excitatory proteins. […] Several oncogenes have been implicated in oral carcinogenesis. Aberrant expression of the proto-oncogene epidermal growth factor receptor (EGFR/c-erb 1), members of the ras gene family, c-myc, int-2, hst-1, PRAD-1, and bcl-1 is believed to contribute towards cancer development.

• #17 Molecular pathogenesis of oral squamous carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1186964/

  Deregulation of growth factors occurs during oral carcinogenesis through increased production and autocrine stimulation. […] EGFR, the biological receptor of EGF and TGF- is frequently overexpressed in oral cancers, and this was found to be the result of EGFR gene amplification in 30% of oral cancers. […] During oral carcinogenisis, intracellular messengers might also be intrinsically activated, thereby overriding the necessity for ligand-receptor regulated signals. […] The functional activity of many of these proteins is regulated by receptor activated second messenger pathways, and neutralisation of these genes could result in a cell cycle block, preventing mitogenic and differentiation responses to growth factors. […] The crucial event in the transformation of a premalignant cell to a malignant cell is inactivation of cellular negative regulators—tumour suppressor genes—and is regarded to be a major event leading to the development of malignancy.

• #18 Pathogenesis and Therapy of Oral Carcinogenesis

  https://www.mdpi.com/1422-0067/25/12/6343

  OSCC develops from the epithelium of the oral cavity mucosa under the influence of genetic, epigenetic, and environmental factors, as well as precancerous lesions such as leukoplakia and erythroplakia. Key features of cancer include maintenance of proliferation, evasion of growth suppressors, resistance to cell death, immortality, angiogenesis, invasion, metastasis, deregulation of energy balance, and evasion of destruction by the immune system. […] EGFR plays a key role in oral carcinogenesis by regulating signaling pathways such as MAPK and PI3K and by promoting proliferation and activation of the oncogene cyclin D1. Overexpression of EGFR is associated with poor prognosis in many cancers. […] Numerous studies indicate that factors such as epidermal growth factor, hydrogen, UV radiation, and ionizing radiation can cause translocation of EGFR to the nucleus, where it interacts with numerous transcription factors and influences the activation of genes involved in cell proliferation, tumor progression, and DNA repair.

• #19 Oral squamous cell carcinomas: state of the field and emerging directions | International Journal of Oral Science

  https://www.nature.com/articles/s41368-023-00249-w

  Persistent exposure to these risk factors results in genetic alterations, epigenetic modifications, and a dysregulated tumor microenvironment, all of which contribute to the occurrence and transformation of OPMDs to OSCC. The genetic alterations result in the aberrant activation of oncogenic pathways, such as EGFR, Wnt/-catenin, JAK/STAT, NOTCH, PI3K/AKT/mTOR, MET, and RAS/RAF/MAPK, as well as disruptions of suppressor pathways, such as TP53/RB, p16/Cyclin D1/Rb, which significantly contribute to the progression of OSCC. […] Epigenetic modifications, such as DNA methylation, histone covalent modification, chromatin remodeling, and gene regulation by non-coding RNAs (ncRNAs), participate in OSCC formation and development. […] Overall, Wnt/-catenin signaling has a vital role to play in the formation of oral malignancies.

• #20 Targeting epigenetics: New insights into oral cancer progression and treatment

  https://medicalxpress.com/news/2025-05-epigenetics-insights-oral-cancer-treatment.html

  LSD1, an epigenetic regulator, is crucial in oral squamous cell carcinoma (OSCC) progression by modulating pathways such as STAT3 and CDK7. Inhibiting LSD1, genetically or with agents like SP2509 or Seclidemstat, reverses preneoplastic lesions, reduces tumor growth, enhances CD8+ T cell infiltration, and lowers CTLA4, highlighting LSD1 inhibition as a promising early-stage OSCC therapy. […] The study uncovers the pivotal role of LSD1 in the progression of oral cancer. […] The study demonstrates that LSD1, an epigenetic regulator, plays a central role in the development of OSCC by controlling critical signaling pathways such as STAT3 and CDK7. […] This study’s findings underscore the importance of epigenetic regulation in OSCC progression and highlight the therapeutic potential of LSD1 inhibitors in preventing the transition from preneoplastic lesions to malignant tumors.

• #21 Targeting Epigenetics: New Insights Into Oral Cancer Progression and Treatment | Newswise

  https://www.newswise.com/articles/targeting-epigenetics-new-insights-into-oral-cancer-progression-and-treatment

  The potential mechanism after blocking LSD1 inhibits novel CDK7 phospho-protein networks and STAT3 signaling ultimately promotes CD8+T cell infiltration and activation by relieving CTLA4-mediated immunosuppression […] The new study focuses on lysine-specific demethylase 1 (LSD1), an epigenetic regulator that plays a significant role in OSCC development. […] A study (DOI: 10.1038/s41368-025-00363-x) published in International Journal of Oral Science (2025) on April 17, 2025, uncovers the pivotal role of LSD1 in the progression of oral cancer. […] The study demonstrates that LSD1, an epigenetic regulator, plays a central role in the development of OSCC by controlling critical signaling pathways such as STAT3 and CDK7. […] This study’s findings underscore the importance of epigenetic regulation in OSCC progression and highlight the therapeutic potential of LSD1 inhibitors in preventing the transition from preneoplastic lesions to malignant tumors.

• #22 Oral squamous cell carcinoma: microRNA expression profiling and integrative analyses for elucidation of tumourigenesis mechanism | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-016-0512-8

  The advantages and utility of microRNAs (miRNAs) as diagnostic and prognostic cancer markers is at the vanguard in recent years. […] The differential expression of 10 miRNAs were validated by RT-qPCR (let-7a, let-7d, let-7f and miR-16 were downregulated while miR-29b, miR-142-3p, miR-144, miR-203, and miR-223 were upregulated in OSCC; the expression of miR-1275 was variable in tumours, with high levels associated to regional lymph node invasion; additionally, miR-223 exhibited an association with advanced tumour stage/size). […] Further, the differentially expressed miRNAs may play a role by simultaneously activating genes of PI3K/Akt signaling on one hand and by repressing genes of p53 signaling pathway on the other. […] The identified differentially expressed miRNAs and signaling pathways deregulated in OSCC have implications for the development of novel therapeutic strategies.

• #23 Oral squamous cell carcinoma: microRNA expression profiling and integrative analyses for elucidation of tumourigenesis mechanism | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-016-0512-8

  The present study utilized miRCURY LNA array (Exiqon, Denmark), that contained capture probes for profiling the expression of 726 mature human miRNAs annotated in miRBase v.16.0, 365 miRNAs proprietary to Exiqon, 77 viral miRNAs, and 18 other small RNAs (snoRNAs, snRNAs and rRNA). […] A similar molecular heterogeneity in Indian OSCC unrelated to differentiation subtypes or clinical tumour stage was reported already by a study when a clustering analysis of samples was performed with differentially expressed miRNAs. […] While we faced some complications in obtaining paired normal tissues, previous studies have demonstrated that control tissues amounting to 10 % of the total sample size is adequate. […] Supporting their general tumour suppressive nature, we observed the downregulation of let-7a, let-7b, let-7d, and miR-16 in OSCC.

• #24 Oral squamous cell carcinoma: microRNA expression profiling and integrative analyses for elucidation of tumourigenesis mechanism | Molecular Cancer | Full Text

  https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-016-0512-8

  Our results on the upregulation of miR-142-3p in OSCC agrees well with previous HNSCC studies. […] The association of miR-29b with tumour size, that of miR-29b, miR-142-3p and miR-144 with regional lymph node invasion, and the additional link between miR-142-3p and smoking clearly warrants further confirmation from upcoming studies. […] The downregulated miRNAs targeted genes enriched in the PI3K/Akt signaling thereby activating limitless replication potential. Conversely, the up regulated miRNAs targeted genes enriched in the p53 signaling pathway, the inhibition of which may lead to evasion of apoptosis and defects in cell cycle checkpoints.

• #25 THE ROLE OF THE ORAL MICROBIOME IN ORAL CANCER PATHOGENESIS | Journal of Population Therapeutics and Clinical Pharmacology

  https://jptcp.com/index.php/jptcp/article/view/3988

  This quantitative research explores the intricate relationship between the oral microbiome and oral cancer, aiming to elucidate microbial markers indicative of disease pathogenesis. […] A case-control study involving 120 participants (60 oral cancer cases and 60 controls) revealed a significant reduction in microbial diversity among oral cancer cases, highlighting microbial dysbiosis. […] Next-generation sequencing unveiled differential abundances, with Fusobacterium nucleatum emerging as a potential microbial biomarker significantly associated with oral cancer. […] Functional analysis indicated enrichment in pathways related to inflammation and cell proliferation in cancer cases, implicating the oral microbiome in the local microenvironment. […] Importantly, Fusobacterium nucleatum exhibited diagnostic promise, displaying a fourfold increase in abundance in oral cancer cases. […] The positive correlation between its abundance and disease severity underscores its prognostic potential. […] This study contributes valuable insights into the quantitative aspects of the oral microbiome in oral cancer, paving the way for personalized diagnostic and therapeutic strategies.

• #26 Associations of oral and intestinal florae and serum inflammatory factors with pathogenesis of oral cancer

  https://www.europeanreview.org/article/23595

  Oral and intestinal florae and serum inflammatory factors are associated with the pathogenesis of oral cancer. […] The aim of this study was to explore the effects of oral and intestinal florae and serum inflammatory factors on the pathogenesis of oral cancer.

• #27 THE ROLE OF THE ORAL MICROBIOME IN ORAL CANCER PATHOGENESIS | Journal of Population Therapeutics and Clinical Pharmacology

  https://jptcp.com/index.php/jptcp/article/view/3988

  This quantitative research explores the intricate relationship between the oral microbiome and oral cancer, aiming to elucidate microbial markers indicative of disease pathogenesis. […] A case-control study involving 120 participants (60 oral cancer cases and 60 controls) revealed a significant reduction in microbial diversity among oral cancer cases, highlighting microbial dysbiosis. […] Next-generation sequencing unveiled differential abundances, with Fusobacterium nucleatum emerging as a potential microbial biomarker significantly associated with oral cancer. […] Functional analysis indicated enrichment in pathways related to inflammation and cell proliferation in cancer cases, implicating the oral microbiome in the local microenvironment. […] Importantly, Fusobacterium nucleatum exhibited diagnostic promise, displaying a fourfold increase in abundance in oral cancer cases. […] The positive correlation between its abundance and disease severity underscores its prognostic potential. […] This study contributes valuable insights into the quantitative aspects of the oral microbiome in oral cancer, paving the way for personalized diagnostic and therapeutic strategies.

• #28 THE ROLE OF THE ORAL MICROBIOME IN ORAL CANCER PATHOGENESIS | Journal of Population Therapeutics and Clinical Pharmacology

  https://jptcp.com/index.php/jptcp/article/view/3988

  This quantitative research explores the intricate relationship between the oral microbiome and oral cancer, aiming to elucidate microbial markers indicative of disease pathogenesis. […] A case-control study involving 120 participants (60 oral cancer cases and 60 controls) revealed a significant reduction in microbial diversity among oral cancer cases, highlighting microbial dysbiosis. […] Next-generation sequencing unveiled differential abundances, with Fusobacterium nucleatum emerging as a potential microbial biomarker significantly associated with oral cancer. […] Functional analysis indicated enrichment in pathways related to inflammation and cell proliferation in cancer cases, implicating the oral microbiome in the local microenvironment. […] Importantly, Fusobacterium nucleatum exhibited diagnostic promise, displaying a fourfold increase in abundance in oral cancer cases. […] The positive correlation between its abundance and disease severity underscores its prognostic potential. […] This study contributes valuable insights into the quantitative aspects of the oral microbiome in oral cancer, paving the way for personalized diagnostic and therapeutic strategies.

• #29 Tongue Cancer – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562324/

  Tongue cancer is one of the most common sites of head and neck malignancy. Smoking, drinking alcohol, and, more recently, human papilloma virus infection are recognized as the major risk factors for the development of tongue cancer. […] The two most important independent risk factors for the development of tongue SCCA are heavy smoking and alcohol use. Cigarette smoke contains known carcinogens, mainly nitrosamines, and polycyclic hydrocarbons. Alcohol metabolizes into acetaldehyde, which affects DNA repair. […] A fundamental, albeit simplified concept in oncogenesis, is the overexpression of oncogenes and silencing of tumor suppressor genes. Environmental lifetime exposure of the oral cavity to known carcinogenic agents leads to DNA damage, and the accumulation of genetic events ultimately leads to the development of carcinoma. Despite numerous genetic alterations that have been linked with the development of cancer, we have only begun to scratch the surface in terms of understanding the relationship between these genetic changes and their relative importance in carcinogenesis. Two of the most well-established genetic alterations that lead to tongue cancer, and head and neck squamous cell carcinoma in general, are mutations in the tumor suppressor gene p53 and overexpression of epidermal growth factor receptor (EGFR) oncogene.

• #30

  https://www.tobaccoinduceddiseases.org/Tobacco-and-oral-squamous-cell-carcinoma-a-review-of-carcinogenic-pathways,105844,0,2.html

  Tobacco is one of the most important risk factors for premature death globally. […] A vast quantity of scientific, clinical and epidemiological data shows that tobacco is associated with the development of oral squamous cell carcinoma, and its carcinogenic pathways may be complicated. […] Tobacco as an important risk factor can cause epigenetic alteration of oral epithelial cells, inhibit multiple systemic immune functions of the host, and its toxic metabolites can cause oxidative stress on tissues and induce OSCC. […] It is widely accepted that tobacco is one the most important carcinogenic factors of OSCC, and its carcinogenic pathways may be multifaceted. […] The epigenetic alteration of these genes is a common event in oral malignancy, and is an inchoate change discovered in oral mucosa of these patients. It indicates that epigenetic alteration is of vital importance in tobacco associated oral carcinogenesis.

• #31 Cancers of the Oral Mucosa: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1075729-overview

  Tobacco is a potent risk factor for oral cancer. An interaction occurs between redox-active metals in saliva and the low-reactive free radicals in cigarette smoke. The result may be that saliva loses its antioxidant capacity and instead becomes a potent pro-oxidant milieu. […] DNA repair genes are clearly involved in the pathogenesis of some rare cancers, such as those that occur in association with xeroderma pigmentosum, but, more recently, evidence of defective DNA repair has also been found to underlie some oral SCCs. […] An immune deficiency state may predispose one to a higher risk of developing oral SCC, especially lip cancer.

• #32 Causes of Oral Cancer – Oral Cancer – Dentalcare

  https://www.dentalcare.com/en-us/ce-courses/ce348/causes-of-oral-cancer

  Two separate lines of research converged to unravel the complex series of events that lead to oral cancer. […] The mechanism by which alcohol contributes to oral cancer is not well understood but it probably acts directly on the epithelial cells of the oral mucosa by increasing permeability and through its dehydrating effects. […] The precise oncogenic effects of HSV on the pathogenesis of oral cancers however, have not been established. […] Of interest is the finding that HPV, particularly types 16 and type 18 are, associated with most squamous cell carcinomas of the oropharynx (tonsil) and base of the tongue. […] High risk HPV types (HPV16 and 18) have also been linked to some forms of oral epithelial dysplasia outside of the base of tongue and oropharynx.

• #33 Tongue cancer – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/tongue-cancer/symptoms-causes/syc-20378428

  Tongue cancer starts when healthy cells in the tongue develop changes in their DNA. A cell’s DNA contains the instructions that tell the cell what to do. The changes tell the cells to grow out of control and to continue living when healthy cells would die as part of their natural life cycle. This makes a lot of extra cells. The cells can form a growth, called a tumor. In time, the cells can break away and spread to other areas of the body. […] For some tongue cancers that happen in the throat, human papillomavirus, also called HPV, can be involved. HPV is a common virus that’s transmitted through sexual contact. Tongue cancer in the throat that’s caused by HPV tends to respond better to treatment compared with tongue cancer in the throat that’s not related to HPV.

• #34 Causes of Oral Cancer – Oral Cancer – Dentalcare

  https://www.dentalcare.com/en-us/ce-courses/ce348/causes-of-oral-cancer

  Two separate lines of research converged to unravel the complex series of events that lead to oral cancer. […] The mechanism by which alcohol contributes to oral cancer is not well understood but it probably acts directly on the epithelial cells of the oral mucosa by increasing permeability and through its dehydrating effects. […] The precise oncogenic effects of HSV on the pathogenesis of oral cancers however, have not been established. […] Of interest is the finding that HPV, particularly types 16 and type 18 are, associated with most squamous cell carcinomas of the oropharynx (tonsil) and base of the tongue. […] High risk HPV types (HPV16 and 18) have also been linked to some forms of oral epithelial dysplasia outside of the base of tongue and oropharynx.

• #35 Metastasis from Oral Cancer: An Overview | Cancer Genomics & Proteomics

  https://cgp.iiarjournals.org/content/9/5/329

  Metastasis of oral cancer is a complex process involving detachment of cells from the tumor tissue, regulation of cell motility and invasion, proliferation and evasion through the lymphatic system or blood vessels. […] This process is due to reduced intercellular adhesion of tumor cells as they progress to malignancy because of loss of E-cadherin; they thereby begin to express proteins such as mesenchymal vimentin and N-cadherin, promoting cell elongation and interfering with cell polarity. This morphological transition, called epithelial-mesenchymal transition (EMT) leads to molecular alterations interfering with the behavior of these cells. […] The EMT is believed to play a crucial role in cancer metastasis. EMT type 3 refers to the loss of carcinoma epithelial phenotype and the acquisition of mesenchymal-associated features which play a relevant role in tumor invasion and metastasis.

• #36 Metastasis from Oral Cancer: An Overview | Cancer Genomics & Proteomics

  https://cgp.iiarjournals.org/content/9/5/329

  Metastasis of oral cancer is a complex process involving detachment of cells from the tumor tissue, regulation of cell motility and invasion, proliferation and evasion through the lymphatic system or blood vessels. […] This process is due to reduced intercellular adhesion of tumor cells as they progress to malignancy because of loss of E-cadherin; they thereby begin to express proteins such as mesenchymal vimentin and N-cadherin, promoting cell elongation and interfering with cell polarity. This morphological transition, called epithelial-mesenchymal transition (EMT) leads to molecular alterations interfering with the behavior of these cells. […] The EMT is believed to play a crucial role in cancer metastasis. EMT type 3 refers to the loss of carcinoma epithelial phenotype and the acquisition of mesenchymal-associated features which play a relevant role in tumor invasion and metastasis.

• #37 Matrix Metalloproteinases in Oral Cancer Pathogenesis and their Use in Therapy – Maurya – Anti-Cancer Agents in Medicinal Chemistry

  https://vietnamjournal.ru/1871-5206/article/view/643671

  Matrix metalloproteinases (MMPs) are proteolytic enzymes that aid in extracellular matrix (ECM) remodeling. MMPs destroy the extracellular matrix, causing tumor growth and metastasis. MMPs are involved in the spread and metastasis of oral cancer. High levels of MMPs and oral squamous cell carcinoma have been linked to cancer prognosis. Modern medicine aims to prevent the illness from spreading through early intervention and examining changes in MMP genes. MMP gene polymorphism has recently been identified as one of the factors predicting susceptibility or risk in the development of oral carcinoma. This review aims to provide insight into the function of MMP subtypes involved in cancer. The genetic polymorphism in MMP genes and its predictive value in risk evaluation have been elaborated. Novel personalized therapeutic approaches for oral cancer, like the use of MMP inhibitors, nanoparticle-mediated targeting of MMP, or gene silencing by microRNA, can be designed. […] Matrix metalloproteinases and their inhibitors: Correlation with invasion and metastasis in oral cancer.

• #38 Metastasis from Oral Cancer: An Overview | Cancer Genomics & Proteomics

  https://cgp.iiarjournals.org/content/9/5/329

  Focal adhesion kinases (FAKs) are protein tyrosine kinases localized in the focal adhesions, which upon activation, interact with each other, regulating several cellular signaling pathways implicated in malignant transformation and disease progression. […] Tumor invasion is thought to involve the multiple proteolytic enzymes, among which are the matrix metalloproteinases (MMPs). MMPs are a family of proteases commonly expressed in invasive tumors and the adjacent stroma and it are thought to play an important role in tumor invasion and metastasis.

• #39 miR-944/MMP10/ AXL- axis Predict Metastasis in Tongue Cancer | Research Communities by Springer Nature

  https://communities.springernature.com/posts/mir-944-mmp10-axl-axis-predict-metastasis-in-tongue-cancer

  Occult lymph node metastases in tongue cancer are associated with significant morbidity and mortality. We describe a novel mechanism wherein miR-944 can regulate MMP10 to activate the AXL signaling pathway in promoting the spread of cancer to the lymph nodes. […] MMP10, which is upregulated in 86% of primary tongue tumors with lymph node metastases, is negatively regulated by miR-944 and promotes nodal metastasis in an orthotopic tongue cancer mouse model through the AXL signaling pathway. […] We earlier described Matrix metalloproteinase-10 (MMP10) as significantly upregulated in early-stage tongue tumor samples associated with nodal metastasis. Its overexpression has been linked to invasion, metastasis, and regulation of stemness in specific cancers. […] In this article published in Comms Biology, we found that MMP10 is overexpressed in 86% primary tongue tumors of patients with lymph node metastases. Its expression could be used to identify patients who are unlikely to benefit from elective neck dissection, as they are unlikely to have lymph node metastases, and thus avoid the invasive surgical procedure and associated morbidity.

• #40 miR-944/MMP10/ AXL- axis Predict Metastasis in Tongue Cancer | Research Communities by Springer Nature

  https://communities.springernature.com/posts/mir-944-mmp10-axl-axis-predict-metastasis-in-tongue-cancer

  Occult lymph node metastases in tongue cancer are associated with significant morbidity and mortality. We describe a novel mechanism wherein miR-944 can regulate MMP10 to activate the AXL signaling pathway in promoting the spread of cancer to the lymph nodes. […] MMP10, which is upregulated in 86% of primary tongue tumors with lymph node metastases, is negatively regulated by miR-944 and promotes nodal metastasis in an orthotopic tongue cancer mouse model through the AXL signaling pathway. […] We earlier described Matrix metalloproteinase-10 (MMP10) as significantly upregulated in early-stage tongue tumor samples associated with nodal metastasis. Its overexpression has been linked to invasion, metastasis, and regulation of stemness in specific cancers. […] In this article published in Comms Biology, we found that MMP10 is overexpressed in 86% primary tongue tumors of patients with lymph node metastases. Its expression could be used to identify patients who are unlikely to benefit from elective neck dissection, as they are unlikely to have lymph node metastases, and thus avoid the invasive surgical procedure and associated morbidity.

• #41 miR-944/MMP10/ AXL- axis Predict Metastasis in Tongue Cancer | Research Communities by Springer Nature

  https://communities.springernature.com/posts/mir-944-mmp10-axl-axis-predict-metastasis-in-tongue-cancer

  Importantly, a false negative rate of 14% means that there is still a possibility that some patients with MMP10 expression within normal ranges could still have lymph node metastases. […] We also found that miR-944 is downregulated in node-positive tongue tumors and that it negatively regulates MMP10 expression by targeting its 3′-UTR. Additionally, we found that MMP10 knockdown or miR-944 overexpression suppresses the proliferation, migration, and invasion of tongue cancer cells and that depletion of MMP10 in an orthotopic tongue cancer mouse model prevents nodal and distant metastases. On the other hand, overexpression of MMP10 leads to the opposite effect by upregulating the epithelial-mesenchymal transition through the activation of the gene, AXL, promoting nodal and distant metastasis in vivo.

• #42 Nerves in Oral Cancer: Mechanism of Interaction and Clinical Relevance

  https://deepblue.lib.umich.edu/handle/2027.42/174397

  Patients with oral squamous cell carcinoma, the most common oral cancer, survive poorly. […] Importantly, these criteria do not integrate the biology of cancer-nerve interactions. […] To address these knowledge gaps, we investigated the clinical significance of PNI and other neural phenotypes in oral cancer, and investigated the underlying mechanisms. Understanding how these mechanisms contribute to clinical outcomes is crucial for developing new treatment strategies to improve survival of patients with oral cancer. […] Our results from tumor specimens of 142 patients with oral cancer, demonstrate that PNI is an independent predictor of poor prognosis. […] Clinical studies on the neural influence in oral cancer were integrated with mechanistic studies. […] Together these studies show that multiple neural phenotypes including PNI, nerve-tumor distance, nerve diameter, and nerve density, are of clinical significance in progression of oral cancer.

• #43 Nerves in Oral Cancer: Mechanism of Interaction and Clinical Relevance

  https://deepblue.lib.umich.edu/handle/2027.42/174397

  To understand the mechanisms of communication between nerves and tumor, we first identified the type(s) of innervation associated with oral cancer, and then performed RNA sequencing and validation studies in vitro and in animal models. […] Interestingly, we previously showed that galanin induces progression of oral cancer via proliferation, invasion, and angiogenesis. […] Here we identified the mechanism by which cancer cells induce galanin release from neurons. […] Together, these findings show that cancer induces a regenerative phenotype in nerves. […] In conclusion, interactions between oral cancer and nerves are governed by an injury-like mechanism that is dependent on nerve-tumor distance, with implications for both prognosis and treatment.

• #44 Nerves in Oral Cancer: Mechanism of Interaction and Clinical Relevance

  https://deepblue.lib.umich.edu/handle/2027.42/174397

  To understand the mechanisms of communication between nerves and tumor, we first identified the type(s) of innervation associated with oral cancer, and then performed RNA sequencing and validation studies in vitro and in animal models. […] Interestingly, we previously showed that galanin induces progression of oral cancer via proliferation, invasion, and angiogenesis. […] Here we identified the mechanism by which cancer cells induce galanin release from neurons. […] Together, these findings show that cancer induces a regenerative phenotype in nerves. […] In conclusion, interactions between oral cancer and nerves are governed by an injury-like mechanism that is dependent on nerve-tumor distance, with implications for both prognosis and treatment.

• #45 Stem-like Cells Proteome Holds Clues to Pathogenesis of Oral Cancer?

  https://www.thermofisher.com/blog/proteomics/does-the-stem-like-cell-proteome-hold-clues-to-the-pathogenesis-of-oral-cancer/

  Oral squamous cell carcinoma is yet another common cancer with typically late presentation, high recurrence after treatment and a poor five-year survival rate. […] One factor thought to contribute to these dire statistics is the presence of sub-populations of cancer stem-like cells (CSCs) within a tumor. These cells are thought to be involved in tumor initiation and growth, metastatic spread, resistance to chemotherapy and tissue invasion. […] The authors suggest that differential levels of protein expression in their proteome (as compared with the non-CSC UM1 cells) could explain the malignant phenotype commonly seen with other CSCs. […] Misuno et al. are confident that their results show potential for further investigation of oral cancer pathogenesis and offer clues for developing therapeutic interventions.

• #46 Stem-like Cells Proteome Holds Clues to Pathogenesis of Oral Cancer?

  https://www.thermofisher.com/blog/proteomics/does-the-stem-like-cell-proteome-hold-clues-to-the-pathogenesis-of-oral-cancer/

  Oral squamous cell carcinoma is yet another common cancer with typically late presentation, high recurrence after treatment and a poor five-year survival rate. […] One factor thought to contribute to these dire statistics is the presence of sub-populations of cancer stem-like cells (CSCs) within a tumor. These cells are thought to be involved in tumor initiation and growth, metastatic spread, resistance to chemotherapy and tissue invasion. […] The authors suggest that differential levels of protein expression in their proteome (as compared with the non-CSC UM1 cells) could explain the malignant phenotype commonly seen with other CSCs. […] Misuno et al. are confident that their results show potential for further investigation of oral cancer pathogenesis and offer clues for developing therapeutic interventions.

• #47 Revealing molecular mechanisms of early-onset tongue cancer by spatial transcriptomics | Scientific Reports

  https://www.nature.com/articles/s41598-024-76044-2

  Tongue cancer at a young age demonstrates an increase in incidence, aggressiveness, and poor response to therapy. Classic etiological factors for head and neck tumors such as tobacco, alcohol, and human papillomavirus are not related to early-onset tongue cancer. Mechanisms of development and progression of this cancer remain unclear. […] Oxidative stress, vascular mimicry, and MAPK and JAK-STAT pathways were enriched in early-onset tongue cancer. […] Taken together, these results indicate that early-onset tongue cancer has distinct transcriptomic features and molecular mechanisms compared to older patients. […] The mechanisms of early-onset TSCC are unclear due to a lack of complex investigation of tumor and microenvironment cell compartments. […] Unlike older patients, TSCC of young adults was found to be enriched with immunosuppressive gene signature, oxidative stress, the MAPK and JAK-STAT molecular pathways, as well as with plasma cells, TAMs and vascular mimicry features at the invasive front.

• #48 THE ROLE OF TUMOR-ASSOCIATED MACROPHAGES IN THE PATHOGENESIS OF ORAL SQUAMOUS CELL CARCINOMA CORRELATED WITH THE CLINICOPATHOLOGICAL PARAMETERS

  https://journals.ekb.eg/article_82702.html

  Oral squamous cell carcinoma (OSCC) accounts for 90-95% of all oral malignancies. […] The inflammatory cells and their signals are indispensable participants in the neoplastic process, fostering proliferation, survival, and migration of cancer cells. […] The macrophages are the most abundant and important stromal cells in the TME, which orchestrate the inflammatory response. […] CD163 was expressed in human OSCC and the TAMs count was significantly correlated with lymph node metastasis and with the tumor differentiation. […] Higher density was detected in metastatic tumors and in the poorly differentiated OSCC than in the well and moderately differentiated cases. […] CD163 positive TAMs could be a prognostic factor in OSCC cases as TAM density was significantly correlated with the lymph node status and the grade of differentiation of OSCC.

• #49

  https://link.springer.com/article/10.1007/s12013-023-01191-8

  Toll-like receptors have been implicated in the development of cancer. […] Certain polymorphisms in toll-like receptor can make a cell more susceptible to develop oral cancer. […] The study revealed that toll-like receptors like TLR7 and TLR5 are found to have a role in suppression of oral cancer while toll-like receptors like TLR4 and TLR2 are found to be associated with the progression of oral cancer. […] Toll-like receptors can turn out as important target molecules in the future in designing therapeutic strategies for oral cancer.

• #50

  https://link.springer.com/article/10.1007/s12013-023-01191-8

  Toll-like receptors have been implicated in the development of cancer. […] Certain polymorphisms in toll-like receptor can make a cell more susceptible to develop oral cancer. […] The study revealed that toll-like receptors like TLR7 and TLR5 are found to have a role in suppression of oral cancer while toll-like receptors like TLR4 and TLR2 are found to be associated with the progression of oral cancer. […] Toll-like receptors can turn out as important target molecules in the future in designing therapeutic strategies for oral cancer.

• #51 Oral squamous cell carcinomas: state of the field and emerging directions | International Journal of Oral Science

  https://www.nature.com/articles/s41368-023-00249-w

  Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% of oral malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. […] Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ), and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oral mucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involves genetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. […] Understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors, thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC.

• #52 Tongue cancer pathophysiology – wikidoc

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

  Leukoplakia and erythroplakia have the greatest potential for malignant transformation into tongue cancer. […] Genes involved in the pathogenesis of tongue cancer include TP53, c-myc, and erb-b1. […] Leukoplakia is considered a premalignant condition from the chronic irritation of the mucous membranes, resulting in increased rates of epithelial and connective tissue proliferation. […] Erythroplakia is considered as the earliest sign of asymptomatic cancer by Mashberg. […] The carcinogens in tobacco smoke, for example, increase the prevalence and spectrum of TP53 mutations. […] Local tumor recurrence reflects extension of genetically damaged cells beyond the clinical and microscopic boundaries of carcinoma to the margins of surgical resection. […] Tongue cancer constitutes of highly differentiated squamous cells lacking frank cytologic criteria of malignancy with rare mitoses. […] The surface of the lesion is covered with compressed invaginating folds of keratin layers. A stroma-like inflammatory reaction and a blunt pushing margin may be seen.

• #53 Tongue cancer overview – wikidoc

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

  Tongue cancer is cancer that begins in the cells of the tongue. […] Genes involved in the pathogenesis of tongue cancer include TP53, c-myc, and erb-b1. […] Leukoplakia and erythroplakia have the greatest potential for malignant transformation in tongue cancer. […] Tongue cancer constitutes of highly differentiated squamous cells lacking frank cytologic criteria of malignancy with rare mitoses. […] Tongue cancer is caused by a point mutation in the tumor suppressor gene (TP53). The other oncogenes associated with oral squamous cell cancers of tongue include c-myc and erb-b1.

• #54 Revealing molecular mechanisms of early-onset tongue cancer by spatial transcriptomics | Scientific Reports

  https://www.nature.com/articles/s41598-024-76044-2

  Early-onset TSCC demonstrates extremely downregulated oxidative phosphorylation and upregulated glycolysis, pentose-phosphate pathway, and glutathione metabolism. […] The key molecular player in early-onset TSCC development is most likely the MAPK signaling pathway, which can be activated by immunosuppressive cells and upregulated in response to hypoxia and oxidative stress. […] In addition, the tumor core of early-onset TSCC was enriched by the interaction of urokinase (PLAU) with integrins v5, which are known to activate ERK1/2, a key component of the MAPK signaling pathway. […] The invasive edge of early-onset TSCC was also found to be enriched with vascular mimicry demonstrating upregulation of the JAK-STAT signaling pathway genes and surrounded by TAMs, which may induce or support this process.

• #55 Oral Fenbendazole for Cancer Therapy in Humans and Animals | Anticancer Research

  https://ar.iiarjournals.org/content/44/9/3725

  Fenbendazole exhibits several other mechanisms contributing to its anti-cancer effects, primarily by disrupting energy metabolism. It functions as a microtubule destabilizing agent, impairs proteasomal function, and inhibits glucose metabolism. Glucose, a primary energy source for tumor cells, is metabolized through aerobic glycolysis and delivered across the cell membrane via the GLUT1 transporter. Unlike normal cells, cancer cells perform glycolysis to metabolize glucose to lactate even under aerobic conditions. Although aerobic glycolysis is not an efficient method of supplying energy and appears to produce less ATP than oxidative phosphorylation, it provides essential materials for tumor cell growth, such as nucleotides, amino acids, and lipids. Additionally, the ATP/ADP and NADH/NAD+ ratios in tumor cells remain high, indicating sufficient ATP supply through glycolytic tumor metabolism.

• #56 Oral Fenbendazole for Cancer Therapy in Humans and Animals | Anticancer Research

  https://ar.iiarjournals.org/content/44/9/3725

  Fenbendazole induces mitochondrial translocation of p53, indicating activation of the p53-p21 pathway, which inhibits GLUT transporter expression and prevents glucose uptake in cancer cells. Through p53 activation, fenbendazole is believed to impede hexokinase II (HKII), the first glycolytic pathway enzyme critical for cancer cell growth. Therefore, fenbendazole’s actions on HKII warrant further exploration. Thus, through targeting GLUT1, HKII, and glycolysis, fenbendazole can lead to cancer cell starvation and reverse drug resistance, aiding cancer treatment. […] In addition to glycolysis inhibition, fenbendazole induces apoptosis in cancer cells. In colorectal cancer (CRC) cells, fenbendazole triggers apoptosis through mitochondrial injury and the caspase 3-PARP pathway. In wild-type CRC, fenbendazole activates p53-mediated apoptosis by increasing p53 expression. Additionally, it induces necrosis, autophagy, and ferroptosis. In 5-FU-resistant CRC, fenbendazole triggers apoptosis without affecting p53 expression, likely enhancing p53-independent ferroptosis-augmented apoptosis.

• #57 Oral Fenbendazole for Cancer Therapy in Humans and Animals | Anticancer Research

  https://ar.iiarjournals.org/content/44/9/3725

  Fenbendazole exhibits several other mechanisms contributing to its anti-cancer effects, primarily by disrupting energy metabolism. It functions as a microtubule destabilizing agent, impairs proteasomal function, and inhibits glucose metabolism. Glucose, a primary energy source for tumor cells, is metabolized through aerobic glycolysis and delivered across the cell membrane via the GLUT1 transporter. Unlike normal cells, cancer cells perform glycolysis to metabolize glucose to lactate even under aerobic conditions. Although aerobic glycolysis is not an efficient method of supplying energy and appears to produce less ATP than oxidative phosphorylation, it provides essential materials for tumor cell growth, such as nucleotides, amino acids, and lipids. Additionally, the ATP/ADP and NADH/NAD+ ratios in tumor cells remain high, indicating sufficient ATP supply through glycolytic tumor metabolism.

• #58 Oral Cancer Pain Predicts Likelihood of Cancer Spreading

  https://www.nyu.edu/about/news-publications/news/2020/october/oral-cancer-pain-predicts-likelihood-of-cancer-spreading.html

  Oral cancer is more likely to spread in patients experiencing high levels of pain, according to a team of researchers at New York University (NYU) College of Dentistry that found genetic and cellular clues as to why metastatic oral cancers are so painful. […] Given that patients with metastatic oral cancer experience more pain, we thought that a patients level of pain might help predict metastasis. […] This observation suggests that patients with less pain are at low risk of metastasis, and will rarely benefit from a neck dissection. […] Forty genes were identified that were more highly expressed in painful metastatic cancers, suggesting that they promote metastasis and mediate cancer pain. […] This suggests that exosomes from cancer may be responsible for oral cancer pain. […] The identified genes are targets for therapy aimed at stopping pain and cancer.

• #59 Oral Cancer Pain Predicts Likelihood of Cancer Spreading

  https://www.nyu.edu/about/news-publications/news/2020/october/oral-cancer-pain-predicts-likelihood-of-cancer-spreading.html

  Oral cancer is more likely to spread in patients experiencing high levels of pain, according to a team of researchers at New York University (NYU) College of Dentistry that found genetic and cellular clues as to why metastatic oral cancers are so painful. […] Given that patients with metastatic oral cancer experience more pain, we thought that a patients level of pain might help predict metastasis. […] This observation suggests that patients with less pain are at low risk of metastasis, and will rarely benefit from a neck dissection. […] Forty genes were identified that were more highly expressed in painful metastatic cancers, suggesting that they promote metastasis and mediate cancer pain. […] This suggests that exosomes from cancer may be responsible for oral cancer pain. […] The identified genes are targets for therapy aimed at stopping pain and cancer.

• #60 Oral Cancer Pain Predicts Likelihood of Cancer Spreading

  https://www.nyu.edu/about/news-publications/news/2020/october/oral-cancer-pain-predicts-likelihood-of-cancer-spreading.html

  Oral cancer is more likely to spread in patients experiencing high levels of pain, according to a team of researchers at New York University (NYU) College of Dentistry that found genetic and cellular clues as to why metastatic oral cancers are so painful. […] Given that patients with metastatic oral cancer experience more pain, we thought that a patients level of pain might help predict metastasis. […] This observation suggests that patients with less pain are at low risk of metastasis, and will rarely benefit from a neck dissection. […] Forty genes were identified that were more highly expressed in painful metastatic cancers, suggesting that they promote metastasis and mediate cancer pain. […] This suggests that exosomes from cancer may be responsible for oral cancer pain. […] The identified genes are targets for therapy aimed at stopping pain and cancer.

• #61 Oral squamous cell carcinomas: state of the field and emerging directions | International Journal of Oral Science

  https://www.nature.com/articles/s41368-023-00249-w

  Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% of oral malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. […] Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ), and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oral mucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involves genetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. […] Understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors, thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC.

• #62 Etiology and Pathogenesis of Oral Cancer (EPOC) | Evans Center for Interdisciplinary Biomedical Research

  https://www.bumc.bu.edu/evanscenteribr/the-arcs/recent-past-arc-programs-evolved-into-university-and-or-agency-funded-programs/etiology-and-pathogenesis-of-oral-cancer-epoc/

  Oral squamous cell carcinoma (OSCC) is among the most morbid cancers with poor survival rates, whose incidence is on the rise. The overall goal of this multidisciplinary ARC application is to determine the molecular mechanisms underlying the Etiology and Pathogenesis of Oral Cancer (EPOC), to identify novel biomarkers predictive of disease initiation, progression and morbidity, to evaluate responses to environmental carcinogens and the role of oral microbiome, and to examine the effectiveness of novel therapeutics in preclinical testing using orthotopic nude mouse models of non-metastatic and metastatic tongue cancers. […] Our studies will generate new knowledge of high impact and translational relevance to oral cancer. Further, information derived from these studies will be relevant to other malignancies and provide a platform for future exploration of new biomarkers and therapeutics for other cancers.

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