Human Epidermal Growth Factor Receptors 2, 4, and 1 (EGFR) (HER2, HER4, EGFR)

Human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 4 (HER4), and epidermal growth factor receptor (EGFR) are single-pass transmembrane receptor tyrosine kinases in the HER/ErbB family. They mediate cell signaling in response to ligand binding, activating intracellular pathways related to cell proliferation, survival, and differentiation. EGFR is directly activated by several growth factors, while HER2 has no known direct ligand and functions predominantly through heterodimerization, especially with other HER family members such as EGFR or HER3. HER4 is activated by neuregulins and can form various dimers within the family. Overactivation—by overexpression, amplification, or activating mutation—of these receptors is strongly associated with the development and progression of cancers, making them important drug targets. Targeted therapies include monoclonal antibodies, TKIs, and antibody-drug conjugates, but resistance and toxicity remain clinical challenges[1][2][3][4].

Other names

ErbB2NeuCD340ErbB4ErbB1HER1

Monoclonal antibodies: Bind to extracellular domain, prevent dimerization (e.g., trastuzumab for HER2, cetuximab for EGFR); Small molecule tyrosine kinase inhibitors (TKIs): Inhibit kinase activity in the intracellular domain (e.g., erlotinib, gefitinib, afatinib); Antibody-drug conjugates: Deliver cytotoxic agents to cells expressing the target (e.g., ado-trastuzumab emtansine); Dual targeting: Some drugs disrupt receptor dimerization (e.g., pertuzumab blocks HER2 dimerization interface).