Receptor tyrosine-protein kinase erbB-2 (HER2) (HER2)

Receptor tyrosine-protein kinase erbB-2, commonly known as HER2, is a 185-kDa transmembrane glycoprotein and a member of the epidermal growth factor receptor (EGFR) family (UniProt: P04626). The trastuzumab epitope is a specific structural region located within Domain IV of the HER2 extracellular domain, situated near the cell membrane (PubMed: 12192403). Unlike other ErbB family members, HER2 does not have a known ligand and exists in a constitutively active conformation, allowing it to readily heterodimerize with other receptors to trigger potent downstream signaling via the PI3K/Akt and MAPK pathways (NCBI: Gene ID 2064). Overexpression or gene amplification of HER2 occurs in approximately 15-30% of breast cancers and is associated with increased tumor aggressiveness and poor prognosis (StatPearls: NBK538250). Therapeutic agents targeting the trastuzumab epitope, such as the monoclonal antibody trastuzumab, exert their effects by inhibiting ligand-independent dimerization, preventing the proteolytic cleavage of the extracellular domain, and recruiting immune cells to induce antibody-dependent cellular cytotoxicity (ADCC) (DrugBank: DB00072). These interventions have significantly improved clinical outcomes for patients with HER2-positive malignancies, although monitoring for potential cardiotoxicity remains a critical safety consideration during treatment.

Other names

ERBB2CD340Proto-oncogene NeuNEUMLN 19Human epidermal growth factor receptor 2

Binding to Domain IV of the HER2 extracellular domain to inhibit ligand-independent dimerization, prevent proteolytic cleavage (shedding) of the extracellular domain, and mediate antibody-dependent cellular cytotoxicity (ADCC) (PubMed: 12192403, DrugBank: DB00072).