title: Ras oncogenes in oral cancer: the past 20 years.
abstract: Oral squamous cell carcinoma (OSCC) of head and neck is associated with high morbidity and mortality in both Western and Asian countries. Several risk factors for the development of oral cancer are very well established, including tobacco chewing, betel quid, smoking, alcohol drinking and human papilloma virus (HPV) infection. Apart from these risk factors, many genetic factors such as oncogenes, tumor suppressor genes and regulatory genes are identified to involve in oral carcinogenesis with these risk factors dependent and independent manner. Ras is one of the most frequently genetically deregulated oncogene in oral cancer. In this review, we analyze the past 22years of literature on genetic alterations such as mutations and amplifications of the isoforms of the ras oncogene in oral cancer. Further, we addressed the isoform-specific role of the ras in oral carcinogenesis. We also discussed how targeting the Akt and MEK, downstream effectors of the PI3K/Akt and MAPK pathways, respectively, would probably pave the possible molecular therapeutic target for the ras driven tumorigenesis in oral cancer. Analysis of these ras isoforms may critically enlighten specific role of a particular ras isoform in oral carcinogenesis, enhance prognosis and pave the way for isoform-specific molecular targeted therapy in OSCC.
authors.affiliation: Department of Molecular Cellular Oncology and Microbiology, Tokyo Medical and Dental University, Tokyo, Japan. amuruga1@jhmi.edu
authors.forename: Avaniyapuram Kannan
authors.initials: AK
authors.lastname: Murugan
authors.forename: Arasambattu Kannan
authors.initials: AK
authors.lastname: Munirajan
authors.forename: Nobuo
authors.initials: N
authors.lastname: Tsuchida
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D005784:Gene Amplification; D011905:Genes, ras / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D009062:Mouth Neoplasms / Q000235:genetics*; D009154:Mutation; D027383:Papillomaviridae; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014030:Tobacco, Smokeless / Q000009:adverse effects
chemical_list: D051057:Proto-Oncogene Proteins c-akt