Tyrosine-protein kinase erbB-2 (HER2)

Tyrosine-protein kinase erbB-2 (commonly known as HER2) is a cell membrane-bound receptor tyrosine kinase encoded by the ERBB2 gene, belonging to the EGFR/ERBB receptor family[1][3]. Unlike other ERBB family members, HER2 has no known ligand and becomes functionally active mainly through dimerization with other ERBB family members, such as EGFR (erbB-1) or HER3 (erbB-3)[1][2]. Upon dimerization, HER2 undergoes autophosphorylation, activating intracellular signaling pathways—such as MAPK and PI3K/Akt—that drive cell proliferation and inhibit apoptosis[1][4]. HER2 is a critical oncogenic driver in several cancers, most notably breast cancer, where ERBB2 gene amplification or HER2 protein overexpression defines a clinically important subtype[1]. HER2 is the target of several clinically approved drugs, including monoclonal antibodies and small-molecule kinase inhibitors, and serves as both a predictive biomarker for response to therapy and a prognostic marker for disease outcome[1][3]. Therapy targeting HER2 has improved survival in patients with HER2-positive cancers, but therapeutic challenges such as acquired resistance and risk of cardiotoxicity remain significant clinical considerations[1][3].

Other names

HER2ErbB-2ERBB2HER-2/neuNeuCD340c-erbB2epidermal growth factor receptor 2v-erb-b2p185neuNEU proto-oncogene

Inhibition of kinase activity (small molecule inhibitors bind to the intracellular kinase domain to block ATP binding and downstream signaling); Antibody-dependent cellular cytotoxicity (monoclonal antibodies binding to HER2 and recruiting immune effectors); Disruption of receptor dimerization (antibodies that prevent heterodimerization of HER2 with other ERBB family receptors); Drug-antibody conjugates delivering cytotoxic payload specifically to HER2-expressing cells