Epidermal growth factor receptor, Human epidermal growth factor receptor 2, Human epidermal growth factor receptor 4 (EGFR, HER2, HER4)

EGFR (ErbB1/HER1), HER2 (ErbB2), and HER4 (ErbB4) are members of the ErbB family of transmembrane receptor tyrosine kinases. They regulate cellular proliferation, survival, and differentiation following activation by growth factors. EGFR and HER4 are activated by direct ligand binding, while HER2 has no known ligand and serves as a preferred dimerization partner for other ErbB family members, notably EGFR and HER3. Ligand binding leads to receptor dimerization (homodimer or heterodimer), autophosphorylation of intracellular tyrosine residues, and downstream signaling via MAPK, PI3K/Akt, and other pathways. Aberrant activation by mutation, amplification, or overexpression drives oncogenesis in multiple human cancers. EGFR and HER2 are established therapeutic targets with approved small-molecule inhibitors and monoclonal antibodies; HER4's role is less well defined but of growing research interest.

Other names

ErbB1HER1Epidermal growth factor receptorErbB2c-erbB2NeuHuman epidermal growth factor receptor 2ErbB4c-erbB4Human epidermal growth factor receptor 4

Inhibition of tyrosine kinase activity (by small molecule inhibitors) Blocking ligand binding and dimerization (by monoclonal antibodies, e.g., trastuzumab, cetuximab) Antibody-drug conjugates deliver cytotoxic agents to HER2-expressing cells Pan-ErbB inhibition may block multiple ErbB receptors