Delineating Genetic Pathways of Disease Progression in Head and Neck Squamous Cell Carcinoma

Abstract

SQUAMOUS CELL carcinoma (SCC) of the head and neck (HNSCC) is the sixth most common malignant disease worldwide. Despite advances in chemotherapy and radiation therapies, HNSCC carries a high mortality rate. The American Joint Committee on Cancer clinical tumor/node/metastasis (TNM) staging system1 is the most important prognosticator of survival at present. Nevertheless, problems with detection of occult metastases in the neck and the fact that tumors with clinically equivalent stages may behave biologically very differently, suggest that additional prognostic markers should be used to supplement TNM staging. Because of the advances of the Human Genome Project, there is presently a unique opportunity to identify new molecular biological markers for this purpose. In addition, study of gene alterations in cancer has led recently to the development of targeted therapies in head and neck cancer, for example, to the use of monoclonal antibodies against overexpressed EGFR (C225).2 Tumor repopulation after treatment, with the regrowth of clones resistant to apoptosis also represents an important challenge to effective long-term therapy for head and neck cancer.3-5 This can be problematic owing to tumor heterogeneity and the fact that standard histological methods can only allow examination of limited cross sections of tumor and surrounding tissue. Identification and analysis of gene changes in cancer may additionally address each of these problems.