Human epidermal growth factor receptor 2 protein (HER2 (also known as ErbB-2, ERBB2, or CD340))

Human epidermal growth factor receptor 2 protein (HER2, also known as ErbB‑2 or ERBB2) is a transmembrane receptor tyrosine kinase encoded by the ERBB2 gene. It belongs to the EGFR/ErbB family of four related receptors found on cell membranes. Unlike other family members, HER2 does not directly bind ligands but becomes activated through dimerization—either with itself at high concentrations or with other EGFR family members—triggering intracellular signaling cascades that promote cell proliferation and survival. In normal tissues, HER2 expression is low; however, amplification or overexpression occurs in approximately one-third of certain aggressive breast cancers and some gastric cancers. This overactivity drives tumorigenesis by constitutively activating proliferative signals even without ligand stimulation. HER2 has become an important therapeutic target and biomarker in oncology. Several monoclonal antibodies (such as trastuzumab and pertuzumab) and small molecule inhibitors have been developed to block its function directly or indirectly. These agents have significantly improved outcomes for patients whose tumors are driven by HER2 overexpression but are associated with specific safety concerns such as cardiotoxicity. Structurally, HER2 consists of an extracellular domain responsible for dimerization, a single-pass transmembrane region anchoring it within the plasma membrane, a juxtamembrane segment linking domains inside the cytoplasm, and an intracellular tyrosine kinase domain responsible for signal propagation via phosphorylation events.

Other names

HER2ErbB-2ERBB2CD340Neu (in rodents)

Drugs act by several mechanisms including: Monoclonal antibodies that block dimerization or signaling (e.g., trastuzumab blocks homodimerization; pertuzumab blocks heterodimerization with other ErbB receptors). Small molecule tyrosine kinase inhibitors that inhibit ATP binding in the kinase domain, blocking downstream signaling pathways essential for cell proliferation and survival.