Molecular progression of head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the most common and fatal cancer type in India with about 30-40% of frequency. Molecular etiologies of the disease include consumption of alcohol, tobacco habit and HPV infection. The lack of understanding in molecular pathogenesis of the disease leads to poor survival of HNSCC patients. Cytogenetic analysis has shown that the chromosomal abnormalities gradually increase with progression of the tumor in a non-random manner. Molecular analysis of-copy number variation, promoter methylation, mutation and expression (gene and protein) revealed identification of some of the candidate tumor suppressor genes located in the chromosomal 3p, 8q, 9p/q, 11q, 13q and 17p etc. regions associated with development of HNSCC. These genes are further seen to control different cellular pathways like-(1) frequent inactivation of SH3GL2 and CDC25A-associated with EGFR homeostasis and de-phosphorylation respectively; (2) Rb and p53 associated pathways in G1-S cell cycle transition; (3) Slit-ROBO associated signaling pathways; (4) PTCH associated Hedgehog signaling; (5) DNA repair pathways like-mismatch and double strand break repair; (6) apoptosis and (7) integrin signaling. Now, systemic approach has been taken to characterize the molecular pathways in this tumor to find out the key regulatory steps for management of the disease.