Epidermal growth factor receptor; Receptor tyrosine-protein kinase erbB-2 (EGFR; HER2)

The epidermal growth factor receptor (EGFR, ERBB1) and receptor tyrosine-protein kinase erbB-2 (HER2, ERBB2) are closely related cell surface receptors belonging to the human epidermal growth factor receptor family (also called the ERBB family), which also includes HER3 (ERBB3) and HER4 (ERBB4). Both are single-pass transmembrane proteins with intrinsic tyrosine kinase activity, involved in regulating signal transduction pathways that control cell growth, proliferation, differentiation, survival, and migration. While EGFR is activated by binding to growth factors such as EGF and TGF-α, HER2 lacks a direct activating ligand and typically becomes active through heterodimerization with other ERBB family members, particularly EGFR and HER3. Overexpression or mutation of these receptors can lead to constitutive pathway activation and is linked to a variety of cancers, especially breast, lung, and gastric cancers. Both EGFR and HER2 are established therapeutic targets, and drugs that inhibit their kinase activity or block receptor dimerization are used as cancer therapies. HER2 expression/amplification serves as an important biomarker in breast and gastric cancer, predicting response to targeted therapy. Resistance to EGFR/HER2-directed treatments commonly arises through receptor mutations or alternative signaling pathway activation, making ongoing molecular monitoring necessary. Note: EGFR and HER2 are distinct gene products and can function independently, but they are closely linked both structurally and therapeutically because of their ability to heterodimerize and initiate potent oncogenic signaling.

Other names

EGFR (HER1, ERBB1)HER2 (ERBB2, Neu, CD340)

Inhibition of tyrosine kinase activity (small molecule inhibitors and antibody–drug conjugates) Antibody-mediated receptor internalization and/or degradation Prevention of receptor dimerization Downregulation of surface receptor density Disruption of downstream signaling pathways (MAPK, PI3K/Akt)