Epidermal growth factor receptor (EGFR), Human epidermal growth factor receptor 2 (HER2), Human epidermal growth factor receptor 4 (HER4) (EGFR (also known as HER1), HER2 (also known as ErbB2), HER4 (also known as ErbB4))

The Epidermal Growth Factor Receptor (EGFR/HER1), Human Epidermal Growth Factor Receptor 2 (HER2/ErbB2), and Human Epidermal Growth Factor Receptor 4 (HER4/ErbB4) are members of the ErbB/HER family of receptor tyrosine kinases, which also includes HER3/ErbB3. They share a common structure: an extracellular ligand-binding domain, a single-pass transmembrane region, and an intracellular tyrosine kinase domain. Upon ligand binding, EGFR and HER4 can homodimerize or heterodimerize with the other HER receptors (particularly HER2, which has no ligand but is always in a dimer-ready state). Dimerization leads to cross-phosphorylation of intracellular tyrosine residues, activating multiple downstream signaling pathways such as MAPK, PI3K-AKT, and JAK/STAT, which regulate cell proliferation, differentiation, survival, and other processes. Dysregulation of these receptors, especially via overexpression or mutation, drives many cancers, making them important therapeutic targets. Numerous small molecule inhibitors and monoclonal antibodies have been developed against EGFR and HER2, while HER4 plays more complex roles and is less commonly targeted, though structurally and functionally related.

Other names

ErbB1HER1Epidermal growth factor receptorErbB2neu (rodents)Human epidermal growth factor receptor 2ErbB4Human epidermal growth factor receptor 4

Tyrosine kinase inhibitors (block ATP binding at the kinase domain, preventing receptor autophosphorylation) Monoclonal antibodies (block ligand binding, induce receptor internalization/degradation, or prevent dimerization) Antibody–drug conjugates (targeted cytotoxic delivery to receptor-positive cells)