ERBB2

About ERBB2

ERBB2, also called HER2, on chromosome 17q12 encodes a receptor tyrosine kinase of the epidermal growth factor receptor family. HER2 has no known ligand of its own but is the preferred dimerization partner for other ErbB receptors, strongly activating PI3K AKT and MAPK signaling. ERBB2 amplification and protein overexpression occur in about 15 to 20 percent of breast cancers, defining the HER2 positive subtype, as well as in a subset of gastric, gastroesophageal, and other cancers. Before targeted therapy, HER2 positive breast cancer was associated with aggressive behavior and poor prognosis, as described by Dennis Slamon and colleagues in 1987. Trastuzumab, a monoclonal antibody against HER2, was approved in 1998 and transformed outcomes. Later agents include pertuzumab, which blocks HER2 dimerization, and antibody drug conjugates such as trastuzumab emtansine and trastuzumab deruxtecan, the latter also active in breast cancers with lower HER2 expression, defining a new HER2 low category. Small molecule inhibitors include lapatinib, neratinib, and tucatinib, which has activity against brain metastases. HER2 status is assessed by immunohistochemistry and in situ hybridization. Activating ERBB2 mutations without amplification occur in lung and other cancers and can also be targeted. The rat counterpart, called neu, was first identified in neuroblastomas induced in rats.