ERBB2HER2

ERBB2, also known as HER2 (human epidermal growth factor receptor 2) or Neu in some species, is a member of the ErbB family of receptor tyrosine kinases. The ERBB2 gene is located on chromosome 17q12 and encodes the HER2 protein, a transmembrane receptor with an extracellular domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. Unlike other ErbB receptors, HER2 lacks a clearly defined high‑affinity ligand and functions as an important co‑receptor. It readily forms homo- or heterodimers with other ErbB receptors, enabling signaling through RAS–MAPK and PI3K–AKT pathways that regulate growth and survival.

ERBB2 amplification or overexpression occurs in about 15–20% of breast cancers and is associated with higher tumor aggressiveness and worse prognosis. It is also found in gastric, ovarian, and other cancers. Diagnosis uses immunohistochemistry (IHC) to assess HER2 protein and fluorescence in situ hybridization (FISH) to detect gene amplification; IHC 3+ is positive, 0–1+ negative, and 2+ equivocal pending FISH.

Therapeutically, HER2-positive status informs treatment with HER2-targeted therapies, often with chemotherapy. Treatments include monoclonal antibodies such as trastuzumab and pertuzumab, antibody–drug conjugates like trastuzumab emtansine, and small‑molecule inhibitors such as lapatinib, neratinib, and tucatinib.

Resistance can arise through multiple mechanisms, including downstream alterations (PI3K pathway mutations) and truncated HER2 forms, motivating ongoing research into new approaches.