Molecular targeted therapies in head and neck cancer

Abstract

Molecular targeted therapies for head and neck cancer offer promising opportunities to improve on the clinical outcomes of conventional treatments. The toxicity profiles of these agents are unique, reflecting their distinct mechanisms of action, and generally do not directly overlap the toxicities of conventional treatment modalities. In this chapter, we review the role of specific molecular targets in head and neck cancer and discuss the development and clinical testing of therapeutics that specifically target these molecules. We focus particularly on the epidermal growth factor receptor (EGFR) and explore the phase III clinical trial data demonstrating a survival benefit with the use of the anti-EGFR antibody, cetuximab, in locally advanced and recurrent/metastatic head and neck cancer. We further discuss the clinical investigation of small-molecule inhibitors of EGFR and other tyrosine kinases as well as current approaches to modulating angiogenesis for therapeutic effect in the context of head and neck cancer. We evaluate novel toxicities associated with molecular targeted therapies that have entered clinical practice and discuss next-generation approaches to molecular targeting. This chapter highlights the promise of molecular targeted therapeutics in head and neck cancer and the potential clinical rewards to be gained from continued investment in the preclinical and clinical investigation of these agents.