EPIDERMAL GROWTH FACTOR RECEPTOR

EGFR (HER1, ErbB1) is an RTK expressed on the surface of cells of mesodermal and ectodermal origin, and it mediates cell growth, proliferation, and differentiation in numerous organs [16, 17]. EGFR belongs to the ErbB family of RTKs, which also includes HER2 (ErbB2), HER3 (ErbB3), and HER4 (ErbB4). EGFR binds at least seven highly variable growth factor ligands [18]. Upon stimulation, EGFR undergoes combinatorial homo- or hetero-dimerization with one of the proteins of the HER family, thereby activating an expansive signaling network [16, 19, 20]. The EGFR transmembrane protein has a large extracellular component (with 4 domains, ~620 amino acids) that primarily serves as ligand-binding sites and which is anchored by a short helical transmembrane domain to the intracellular tyrosine kinase domain (TKD) (Fig.?1) [18].

EGFR is believed to play a role in the pathogenesis of lung cancer and is overexpressed in a majority of NSCLCs [21, 22]. However, the clinical importance of EGFR expression in the general NSCLC population is unclear. There was some suggestion that EGFR expression may serve as a predictive biomarker [21], but this has been superseded by mutational analysis after the identification of actionable driver mutations in the EGFR gene.