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Nature Reviews. Disease Primers Nov 2020Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell... (Review)
Review
Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, whereas pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV), primarily HPV-16. Thus, HNSCC can be separated into HPV-negative and HPV-positive HNSCC. Despite evidence of histological progression from cellular atypia through various degrees of dysplasia, ultimately leading to invasive HNSCC, most patients are diagnosed with late-stage HNSCC without a clinically evident antecedent pre-malignant lesion. Traditional staging of HNSCC using the tumour-node-metastasis system has been supplemented by the 2017 AJCC/UICC staging system, which incorporates additional information relevant to HPV-positive disease. Treatment is generally multimodal, consisting of surgery followed by chemoradiotherapy (CRT) for oral cavity cancers and primary CRT for pharynx and larynx cancers. The EGFR monoclonal antibody cetuximab is generally used in combination with radiation in HPV-negative HNSCC where comorbidities prevent the use of cytotoxic chemotherapy. The FDA approved the immune checkpoint inhibitors pembrolizumab and nivolumab for treatment of recurrent or metastatic HNSCC and pembrolizumab as primary treatment for unresectable disease. Elucidation of the molecular genetic landscape of HNSCC over the past decade has revealed new opportunities for therapeutic intervention. Ongoing efforts aim to integrate our understanding of HNSCC biology and immunobiology to identify predictive biomarkers that will enable delivery of the most effective, least-toxic therapies.
Topics: Human papillomavirus 16; Humans; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck; Tobacco Use
PubMed: 33243986
DOI: 10.1038/s41572-020-00224-3 -
Medical Sciences (Basel, Switzerland) Jun 2023Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies, involving the oral cavity, pharynx, hypopharynx, larynx, nasal cavity, and salivary glands,... (Review)
Review
Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies, involving the oral cavity, pharynx, hypopharynx, larynx, nasal cavity, and salivary glands, that together compose the seventh most common cancer diagnosis worldwide. With 890,000 new cases and 450,000 deaths annually per GLOBOCAN estimates, HNSCC accounts for roughly 4.5% of cancer diagnoses and deaths. In the developing world, the incidence of HNSCC is growing with increasing consumption of tobacco (smoked or chewed), alcohol, and areca nut (betel quid). Alcohol and tobacco have a synergistic effect, with the heavy consumption of both increasing HNSCC risk 40-fold. In developed nations, HPV-related HNSCC surpasses tobacco- and alcohol-related disease. HPV-related HNSCC more commonly affects the oropharynx, hypopharynx, and larynx than the oral cavity, and is associated with a significantly longer median survival (130 months vs. 20 months). Discrepancies in etiology as well as disparities in lifestyle choices and access to healthcare may account for the greater incidence and poorer survival of HNSCC among minority and lower-socioeconomic-status communities in developed nations. Pharmacotherapy and counseling together have been shown to be effective in promoting smoking and alcohol cessation. Education on cancer risk and community engagement have reduced areca nut consumption in Asia as well as in diaspora communities. HPV vaccination, starting at age 11-12 for both sexes, has been shown to reduce the prevalence of high-risk HPV serologies and prevent pre-cancerous lesions of the cervix, vagina, and vulva. As of 2020, 58.6% of eligible adolescents in the US have received the full two-vaccine series. Increased adoption of vaccination, education on safe sex practices, and routine visual oral screening for high-risk patients would curb growing HNSCC incidence in developed nations.
Topics: Male; Female; Humans; Adolescent; Child; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Papillomavirus Infections; Risk Factors
PubMed: 37367741
DOI: 10.3390/medsci11020042 -
Annals of Oncology : Official Journal... Nov 2020
Topics: Carcinoma, Squamous Cell; Follow-Up Studies; Head and Neck Neoplasms; Humans; Hypopharynx; Larynx; Mouth; Oropharynx
PubMed: 33239190
DOI: 10.1016/j.annonc.2020.07.011 -
Molecular Cancer Jan 2022Head and neck cancer is the sixth most common cancer across the globe. This is generally associated with tobacco and alcohol consumption. Cancer in the pharynx majorly... (Review)
Review
Head and neck cancer is the sixth most common cancer across the globe. This is generally associated with tobacco and alcohol consumption. Cancer in the pharynx majorly arises through human papillomavirus (HPV) infection, thus classifying head and neck squamous cell carcinoma (HNSCC) into HPV-positive and HPV-negative HNSCCs. Aberrant, mesenchymal-epithelial transition factor (c-MET) signal transduction favors HNSCC progression by stimulating proliferation, motility, invasiveness, morphogenesis, and angiogenesis. c-MET upregulation can be found in the majority of head and neck squamous cell carcinomas. c-MET pathway acts on several downstream effectors including phospholipase C gamma (PLCγ), cellular Src kinase (c-Src), phosphotidylinsitol-3-OH kinase (PI3K), alpha serine/threonine-protein kinase (Akt), mitogen-activated protein kinase (MAPK), and wingless-related integration site (Wnt) pathways. c-MET also establishes a crosstalk pathway with epidermal growth factor receptor (EGFR) and contributes towards chemoresistance in HNSCC. In recent years, the signaling communications of c-MET/HGF in metabolic dysregulation, tumor-microenvironment and immune modulation in HNSCC have emerged. Several clinical trials have been established against c-MET/ hepatocyte growth factor (HGF) signaling network to bring up targeted and effective therapeutic strategies against HNSCC. In this review, we discuss the molecular mechanism(s) and current understanding of c-MET/HGF signaling and its effect on HNSCC.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Disease Management; Disease Susceptibility; Drug Resistance, Neoplasm; Energy Metabolism; Head and Neck Neoplasms; Hepatocyte Growth Factor; Humans; Immunity; Proto-Oncogene Proteins c-met; Signal Transduction; Treatment Outcome; Tumor Microenvironment
PubMed: 35081970
DOI: 10.1186/s12943-022-01503-1 -
Molecular Cancer Therapeutics Dec 2023Integrin beta-6, a component of the heterodimeric adhesion receptor alpha-v/beta-6, is overexpressed in numerous solid tumors. Its expression has been shown by multiple...
Integrin beta-6, a component of the heterodimeric adhesion receptor alpha-v/beta-6, is overexpressed in numerous solid tumors. Its expression has been shown by multiple investigators to be a negative prognostic indicator in diverse cancers including colorectal, non-small cell lung, gastric, and cervical. We developed SGN-B6A as an antibody-drug conjugate (ADC) directed to integrin beta-6 to deliver the clinically validated payload monomethyl auristatin E (MMAE) to cancer cells. The antibody component of SGN-B6A is specific for integrin beta-6 and does not bind other alpha-v family members. In preclinical studies, this ADC has demonstrated activity in vivo in models derived from non-small cell lung, pancreatic, pharyngeal, and bladder carcinomas spanning a range of antigen expression levels. In nonclinical toxicology studies in cynomolgus monkeys, doses of up to 5 mg/kg weekly for four doses or 6 mg/kg every 3 weeks for two doses were tolerated. Hematologic toxicities typical of MMAE ADCs were dose limiting, and no significant target-mediated toxicity was observed. A phase I first-in-human study is in progress to evaluate the safety and antitumor activity of SGN-B6A in a variety of solid tumors known to express integrin beta-6 (NCT04389632).
Topics: Humans; Immunoconjugates; Antineoplastic Agents; Prognosis; Integrins; Carcinoma; Cell Line, Tumor
PubMed: 37619980
DOI: 10.1158/1535-7163.MCT-22-0817 -
Cell Death and Differentiation Jun 2022As the most predominant RNA epigenetic regulation in eukaryotic cells, N-methyladenosine (mA) plays a critical role in human tumorigenesis and cancer progression....
As the most predominant RNA epigenetic regulation in eukaryotic cells, N-methyladenosine (mA) plays a critical role in human tumorigenesis and cancer progression. However, the biological function and molecular mechanism of mA regulation in naso-pharyngeal carcinoma (NPC) remain elusive. Here, we showed that Wilms' tumor 1-associating protein (WTAP) expression was apparently upregulated in NPC, and increased WTAP was associated with poor prognosis. WTAP upregulated in NPC was fine-tuned by KAT3A-mediated H3K27 acetylation. Functionally, WTAP was required for the growth and metastasis of NPC. Mechanistically, lncRNA DIAPH1-AS1 was identified as a bona fide mA target of WTAP. WTAP-mediated mA modification of DIAPH1-AS1 enhanced its stability relying on the mA reader IGF2BP2-dependent pathway. Furthermore, DIAPH1-AS1 acted as a molecular adaptor that promoted MTDH-LASP1 complex formation and upregulated LASP1 expression, ultimately facilitating NPC growth and metastasis. Thus, WTAP-mediated DIAPH1-AS1 mA methylation is required for NPC tumorigenesis and metastasis.
Topics: Adaptor Proteins, Signal Transducing; Adenosine; Carcinogenesis; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cytoskeletal Proteins; Epigenesis, Genetic; Formins; Humans; LIM Domain Proteins; Membrane Proteins; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Neoplasm Metastasis; RNA Splicing Factors; RNA, Long Noncoding; RNA-Binding Proteins
PubMed: 34999731
DOI: 10.1038/s41418-021-00905-w -
Head and Neck Pathology Mar 2022The new WHO classification of head and neck tumors provides a comprehensive overview of lesions by summarizing their clinical, epidemiological, histological,... (Review)
Review
The new WHO classification of head and neck tumors provides a comprehensive overview of lesions by summarizing their clinical, epidemiological, histological, immunohistochemical, molecular and genetic features. The chapters related to the description of oropharyngeal and nasopharyngeal lesions have thus been largely modified.
Topics: Head and Neck Neoplasms; Humans; Nasopharynx; Oropharynx; World Health Organization
PubMed: 35312986
DOI: 10.1007/s12105-022-01449-2