Molecular therapy of head and neck cancer

Aberrant expression of growth factor receptor systems and dysregulation of the downstream cell signalling molecules have been reported in a wide range of epithelial tumours including head and neck cancer. In some cases, such alterations have been associated with a poor prognosis. In the past 25 years, several antigen specific monoclonal antibodies (mAbs, mouse, chimeric, humanized and human versions), and small molecule kinase inhibitors have been developed that are at different stages of preclinical and clinical developments. Some of these agents (e.g. Herceptin, Iressa, cetuximab, avastin) have already been approved for the treatment of epithelial tumours and may also have potential in the treatment of head and neck cancer patients. This review discusses, the development and potential of these antigen specific agents, in particular the human epidermal growth factor receptor (EGFR) inhibitors, either as a single agent or in combination with other EGFR inhibitors, biological agents (e.g. inhibitors of cycloogenase-2, angiogenesis, insulin like growth factor-I receptor and others), and conventional forms of therapy in the prevention and treatment of head and neck cancer. From preclinical and clinical studies with some of these compounds, it is evident that further detailed studies of biopsies from cancer patients are needed in order to identify markers that can be used not only in the selection of the specific population of cancer patients who would benefit from such antigen specific therapeutic strategies, but also those factors which are responsible for the poor response and the development of a phenotype resistance to such inhibitors. The results of such studies could in turn facilitate the widespread use of such agents in the treatment of a wide range of human cancers including head and neck cancer.