Epidermal growth factor receptor (EGFR)

Epidermal growth factor receptor is a single-chain transmembrane glycoprotein belonging to the ErbB family of receptors. It consists of an extracellular ligand-binding domain, a single-pass transmembrane region, and an intracellular tyrosine kinase domain. Upon binding ligands such as epidermal growth factor or transforming growth factor alpha, EGFR undergoes dimerization—either as homodimers with itself or heterodimers with other ErbB family members—which activates its intrinsic tyrosine kinase activity. This leads to autophosphorylation on specific intracellular tyrosines and initiates multiple downstream signaling cascades that regulate cell proliferation, differentiation, survival, migration, and development[1][3][5]. Aberrant activation—through overexpression or mutation—is implicated in the pathogenesis of various cancers by driving uncontrolled cell division[2][5]. As such, EGFR is a major therapeutic target; several small molecule inhibitors and monoclonal antibodies have been developed to block its function in oncology[2][5]. Monitoring for activating mutations serves as a biomarker for patient selection. However, treatment can be complicated by resistance mechanisms and notable side effects including dermatologic toxicities[5].

Other names

ErbB1HER1ERBBReceptor tyrosine-protein kinase erbB-1

Inhibition of tyrosine kinase activity (small molecule inhibitors block ATP binding site); Antibody-mediated blockade of ligand binding or receptor dimerization (monoclonal antibodies prevent activation and downstream signaling)