Human epidermal growth factor receptor 2 (HER2) (HER2)

Human epidermal growth factor receptor 2 (HER2), encoded by the ERBB2 gene, is a transmembrane receptor tyrosine kinase and a member of the epidermal growth factor receptor (EGFR) family [1, 4]. Unlike other members of its family, HER2 does not have a known ligand and exists in a constitutively active conformation, allowing it to serve as the preferred dimerization partner for other ErbB receptors [1, 8]. This dimerization activates critical downstream signaling cascades, including the PI3K/AKT and MAPK pathways, which regulate cell growth, survival, and differentiation [5, 6]. In many cancers, most notably breast and gastric malignancies, HER2 is overexpressed or the gene is amplified, driving aggressive tumor behavior and poor prognosis [2, 12]. Because of its high expression on tumor cells compared to normal tissue, HER2 is a major therapeutic target for monoclonal antibodies, tyrosine kinase inhibitors, and antibody-drug conjugates that inhibit its signaling or deliver cytotoxic agents directly to the tumor [7, 13].

Other names

ERBB2CD340Proto-oncogene NeuReceptor tyrosine-protein kinase erbB-2NEUNGLTKR1ErbB2

Inhibition of receptor dimerization, inhibition of intracellular tyrosine kinase activity, induction of antibody-dependent cellular cytotoxicity (ADCC), targeted delivery of cytotoxic payloads via antibody-drug conjugates (ADCs), and inhibition of downstream PI3K/AKT and MAPK signaling pathways.