Abstract
INTRODUCTION: Despite improvements in treatment, survival rates of head and neck squamous cell carcinoma (HNSCC) are stagnant. The existing chemotherapeutic agents are non-selective and associated with toxicities. Combinations of the only the US FDA-approved epidermal growth factor receptor (EGFR)-targeted agent, cetuximab, with chemotherapy or radiation improves overall survival. However, the response rates to cetuximab are modest. Thus, there is an urgent need for new agents that can be safely integrated into current treatment regimens to improve outcome. AREAS COVERED: Current EGFR-targeted drugs under clinical development include mAbs and tyrosine kinase inhibitors. The modest efficacy of these drugs implicates intrinsic or acquired resistance. Novel molecular agents inhibiting alternative targets to overcome anti-EGFR resistance in HNSCC are under investigation. Gene therapy and immunotherapy are also promising strategies to improve efficacy and reduce toxicity. EXPERT OPINION: To date, only six drugs have been FDA-approved for the treatment of head and neck cancer. Cetuximab is the only approved molecular targeting agent for HNSCC and despite ubiquitous expression of EGFR in HNSCC tumors, clinical responses are limited. Genetic and epigenetic characterization of HNSCC tumors, coupled with improved preclinical models, should facilitate the development of more effective drugs.