Epidermal Growth Factor Receptor Targeting in Head and Neck Cancer: Have We Been Just Skimming the Surface?

Despite extensive research in squamous cell carcinoma of the head and neck (SCCHN), the epidermal growth factor receptor (EGFR) remains the only nonchemotherapeuticmolecular target that has been successfully translated into a biologic therapy with clinical benefit. Targeting this transmembrane tyrosine kinase growth factor receptor in SCCHN is an attractive and rational strategy given that more than 90 % of these tumors overexpress EGFR. The potential value of EGFR as a therapeutic target is also supported by the obser-vation that poor prognostic outcomes have been correlated with in-creased EGFR protein expression or EGFR gene copy number amplification.1-3 Traditional anti-EGFR strategies include monoclo-nal antibodies (MABs) that block the extracellular ligand-binding domain and small molecule inhibitors that reversibly inhibit activa-tion of the cytoplasmic tyrosine kinase. Currently, the only approved targeted therapy in SCCHN is cetuximab, the chimeric immunoglob-