Mechanisms of resistance to EGFR inhibitors in head and neck cancer

Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that activates multiple signaling pathways, including phosphatidylinositol-3-kinase/v-AKT murine thymoma viral oncogene homolog protein (Akt), has long been a target of novel therapies. Despite universal EGFR expression in head and neck squamous cell carcinoma (HNSCC), the majority of patients do not respond to EGFR inhibitors. This review focuses on mechanisms of resistance to these agents in HNSCC, and how these may be unique when compared with other malignancies such as non-small cell lung and colorectal cancers. Published studies and abstracts reveal that there are likely several mechanisms underlying resistance, suggesting that different strategies will be required to improve efficacy of EGFR inhibitors in HNSCC.