The molecular pathogenesis of head and neck squamous cell carcinoma

• Published in: The Journal of clinical investigation Vol. 122; no. 6; pp. 1951 - 1957
• Main Authors: Rothenberg, S Michael, Ellisen, Leif W
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.06.2012
• Subjects: Alcohol Drinking - adverse effects; Alcohol Drinking - epidemiology; Alcohol Drinking - genetics; Alcohol Drinking - metabolism; Alphapapillomavirus - genetics; Alphapapillomavirus - metabolism; Apoptosis; Biomedical research; Cancer therapies; Carcinoma, Squamous Cell - epidemiology; Carcinoma, Squamous Cell - etiology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - therapy; Care and treatment; Cell cycle; Cell division; Class I Phosphatidylinositol 3-Kinases; Clinical pathology; Development and progression; Drug Delivery Systems; Genes; Head and neck cancer; Head and Neck Neoplasms - epidemiology; Head and Neck Neoplasms - etiology; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - therapy; Human papillomavirus; Humans; Medical prognosis; Molecular biology; Mutation; Papillomavirus Infections - complications; Papillomavirus Infections - epidemiology; Papillomavirus Infections - genetics; Papillomavirus Infections - metabolism; Pathogenesis; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; ras Proteins - genetics; ras Proteins - metabolism; Risk factors; Science in Medicine; Squamous cell carcinoma; Tobacco Use Disorder - complications; Tobacco Use Disorder - epidemiology; Tobacco Use Disorder - genetics; Tobacco Use Disorder - metabolism; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors; United States
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci59889

Squamous cell carcinoma of the head and neck (HNSCC) is a relatively common human cancer characterized by high morbidity, high mortality, and few therapeutic options outside of surgery, standard cytotoxic chemotherapy, and radiation. Although the most important risk factors are tobacco use and alcohol consumption, the disease is also linked to infection with high-risk types of human papilloma viruses (HPVs). Recent genetic analyses have yielded new insights into the molecular pathogenesis of this disease. Overall, while somatic activating mutations within classical oncogenes including PIK3CA and RAS occur in HNSCC, they are relatively uncommon. Instead genetic data point to a contribution of multiple tumor suppressor pathways, including p53, Rb/INK4/ARF, and Notch, in tumor initiation, progression, and maintenance. The increasingly refined knowledge of HNSCC genetics, combined with ever-more-sophisticated animal models and newer drug targeting strategies, should promote novel therapeutic approaches and improved disease outcomes.