Epidermal growth factor receptor (EGFR)

The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase of the ErbB family, which also includes HER2/ErbB2, HER3/ErbB3, and HER4/ErbB4[6][2]. EGFR is comprised of an extracellular ligand-binding domain, a single-pass transmembrane helix, and an intracellular tyrosine kinase domain[2][4]. Upon binding of ligands such as epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-α), the receptor undergoes conformational change leading to homo- or heterodimerization. This causes activation of its intrinsic kinase activity, resulting in autophosphorylation of specific tyrosine residues on its cytoplasmic tail[4][6]. These phosphotyrosines serve as docking sites for adaptor proteins, activating multiple downstream signaling cascades, including the RAS-RAF-MAPK, PI3K-AKT, and PLCγ-PKC pathways, which regulate diverse biological outcomes such as cell proliferation, survival, migration, and differentiation[2][6]. EGFR is expressed in many epithelial tissues and contributes to normal development and wound healing, but its dysregulation through mutation, overexpression, or aberrant activation is implicated in the pathogenesis of various cancers, including non-small cell lung cancer, colorectal cancer, and head and neck cancers[7][2][6]. Numerous small molecule tyrosine kinase inhibitors and monoclonal antibodies target EGFR, providing both therapeutic options and predictive/prognostic biomarkers in oncology[2][6]. Safety concerns in therapy involve skin toxicity and risk of interstitial lung disease among others. Wild-type EGFR refers specifically to the non-mutant, physiologically normal form of the receptor, as opposed to oncogenic variants harboring activating kinase domain mutations[5][7].

Other names

ErbB-1HER1ERBB1Epidermal growth factor receptor (HER1)ErbB family receptor

Tyrosine kinase inhibition; Monoclonal antibody-mediated receptor blockade; Inhibition of ligand binding; Inhibition of receptor dimerization and signaling; Receptor downregulation via internalization