Targeting the ErbB Family in Head and Neck Cancer

Members of the ErbB receptor tyrosine kinase family (EGFR, HER2, HER3, and HER4), which regulate cell differentiation, proliferation, and survival, are commonly overexpressed and hyperactivated in squamous cell carcinoma of the head and neck (SCCHN). This abnormal expression and activity triggers multiple effector cascades that promote cancer growth, involving signaling through Ras-Raf-ERK1/2, PI3K/AKT/mTOR, JAK1/STAT3, PLC/PKC, and others. Targeting of EGFR remains one of the most common therapies for patients with SCCHN, with newer therapies also targeting additional ErbB family members and ErbB effectors, and exploring combinatorial approaches. In this chapter, we will describe the biology of ErbB family receptors in normal cells and in SCCHN, current and novel therapeutic approaches, and mechanisms underlying resistance to anti-EGFR therapy.