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

Receptor tyrosine-protein kinase erbB-2, commonly known as HER2, is a transmembrane glycoprotein and a member of the epidermal growth factor receptor (EGFR) family [UniProt]. Unlike other ErbB family members, HER2 lacks a known high-affinity ligand-binding domain and instead exists in a constitutively active conformation, serving as the preferred heterodimerization partner for other ligand-bound ErbB receptors [PubMed: 12673233]. This dimerization activates downstream signaling pathways, including the PI3K/Akt and MAPK pathways, which are critical for regulating cell growth, survival, and differentiation [StatPearls]. In various malignancies, most notably breast and gastric cancers, HER2 is frequently overexpressed or the ERBB2 gene is amplified, driving oncogenic transformation and aggressive tumor behavior [NCBI Gene]. Pharmacological targeting of HER2 has revolutionized oncology through the use of monoclonal antibodies that block signaling, small-molecule inhibitors that target the kinase domain, and antibody-drug conjugates that deliver potent chemotherapy directly to HER2-positive cells [PubMed: 32034119]. Clinical management of HER2-positive diseases relies heavily on accurate biomarker testing to identify patients who will benefit from these targeted therapies. Despite the success of HER2-targeted agents, challenges such as acquired resistance and specific toxicities like cardiotoxicity remain significant areas of clinical focus.

Other names

Human epidermal growth factor receptor 2ERBB2NEUCD340Proto-oncogene c-ErbB-2MLN 19Proto-oncogene Neu

Inhibition of receptor dimerization, blockade of intracellular tyrosine kinase activity, induction of antibody-dependent cellular cytotoxicity (ADCC), and targeted delivery of cytotoxic payloads via antibody-drug conjugates (ADCs).