Epidermal growth factor receptor (EGFR) and Human epidermal growth factor receptor 2 (HER2) (EGFR and HER2)

Epidermal growth factor receptor (EGFR, also known as ERBB1 or HER1) and human epidermal growth factor receptor 2 (HER2, also known as ERBB2, Neu, or CD340) are members of the ERBB family of transmembrane receptor tyrosine kinases. These proteins possess an extracellular ligand-binding domain, a single transmembrane region, a juxtamembrane region, and an intracellular tyrosine kinase domain. EGFR binds a variety of ligands (such as EGF and epiregulin), resulting in receptor dimerization and trans-autophosphorylation. HER2, lacking a direct ligand, serves as a preferred dimerization partner for other ERBB receptors—especially EGFR and HER3—and thereby amplifies signaling. Overexpression or activating mutations in either receptor drive uncontrolled cell proliferation and survival, underlying the pathogenesis of many epithelial cancers including breast, lung, and gastric cancers. Both EGFR and HER2 are therapeutic targets: monoclonal antibodies and small molecule inhibitors have become standard-of-care in tumors with activating mutations or overexpression. HER2/EGFR dimer formation has distinct structural features, where HER2’s dimerization arm is critical for assembly and downstream signal propagation, and HER2 may protect EGFR from endocytosis, prolonging oncogenic signaling[1][2][4][5][6][7][8][10].

Other names

ErbB-1ERBB1HER1ErbB-2ERBB2NeuCD340

Inhibition of kinase activity (tyrosine kinase inhibitors block ATP binding, preventing phosphorylation); Antibody-dependent cellular cytotoxicity (monoclonal antibodies bind extracellular domain and recruit immune responses); Prevention of dimerization (antibodies such as pertuzumab block receptor-receptor interaction); Downregulation and internalization (some monoclonal antibodies lead to receptor internalization and degradation)