New Strategies in Head and Neck Cancer: Understanding Resistance to Epidermal Growth Factor Receptor Inhibitors

The epidermal growth factor receptor (EGFR) is a validated target in squamous cell carcinoma of the head and neck (HNSCC). However, despite high expression of EGFR in these cancers, EGFR inhibitor monotherapy has only had modest activity. Potential mechanisms of resistance to EGFR-targeted therapies involve EGFR and Ras mutations, epithelial-mesenchymal transition, and activation of alternative and downstream pathways. Strategies to optimize EGFR-targeted therapy in head and neck cancer involve not only the selection for patients most likely to benefit but also the use of combination therapies to target the network of pathways involved in tumor growth, invasion, angiogenesis, and metastasis. Clin Cancer Res; 16(9); 2489-95. (C) 2010 AACR.