Introduction

Over the last decade two highly specific, robust molecular targets have proven practical and relevant for therapy and prognosis in squamous cell cancers of the head and neck (HNC): the epidermal growth factor receptor (EGFR) and human papillomavirus (HPV). EGFR and its signaling pathways are key regulators of cell growth. The first experimental studies with anti-EGFR antibodies in human tumor models took place 25 years ago, culminating in the approval of an EGFR targeting agent in 2006 as the first new treatment for HNC in over 45 years. Recent studies have also identified HPV as a causative factor in oropharyngeal HNC. If current trends continue, there will soon be over 20 000 cases of HPV-caused oropharynx cancer in the United States. To date, EGFR and HPV are the most clinically relevant molecular targets in HNC.

EGFR expression in HNC

The epidermal growth factor receptor (EGFR) is a member of the ERBB family of tyrosine kinase receptors. EGFR regulates a variety of cellular functions by activating downstream effectors in cellular growth, differentiation, and survival pathways. Other ERBB family members include ERBB2 (HER2, Neu), ERBB3 (HER3), and ERBB4 (HER4). The family members all contain a unique extra-cellular domain along with a transmembrane domain and a tyrosine kinase domain that is structurally conserved across family members, although HER3 is kinase dead (Figure 42.1).