![]() ![]() HER2 has no known direct activating ligand and may be in an activated state constitutively or become active upon heterodimerization with other family members such as HER1 and HER3. Upon ligands binding to their extracellular domains, HER proteins undergo dimerization and transphosphorylation of their intracellular domains. The HER receptors exist as monomers on the cell surface. ![]() HER2 is expressed in many tissues and its major role in these tissues is to facilitate excessive/uncontrolled cell growth and tumorigenesis. The HER2 receptor is a 1255 amino acid, 185âkD transmembrane glycoprotein located at the long arm of human chromosome 17 (17q12). The neu oncogene (also known as HER2, ErbB2, or p185) was discovered by a group of scientists at Massachusetts Institute of Technology, Rockefeller, and Harvard University. ErbB stands for its origin in the Erb-b gene responsible for avian erythroblastosis virus. Epidermal growth factor receptor (EGFR, ErbB1, and HER1)-the first receptor tyrosine kinase, was discovered by Carpenter and coworkers at Vanderbilt University, USA, in 1978. All four HER receptors comprise a cysteine-rich extracellular ligand binding site, a transmembrane lipophilic segment, and an intracellular domain with tyrosine kinase catalytic activity. The family is made up of four main members: HER-1, HER-2, HER-3, and HER-4, also called ErbB1, ErbB2, ErbB3, and ErbB4, respectively. They regulate cell growth, survival, and differentiation via multiple signal transduction pathways and participate in cellular proliferation and differentiation. The human epidermal growth factor receptor (HER) family of receptors plays a central role in the pathogenesis of several human cancers. This review discusses the role of HER2 in various cancers and therapeutic modalities available targeting HER2. The introduction of HER2 directed therapies has dramatically influenced the outcome of patients with HER2 positive breast and gastric/gastroesophageal cancers however, the results have been proved disappointing in other HER2 overexpressing cancers. HER2 overexpression has also been seen in other cancers like ovary, endometrium, bladder, lung, colon, and head and neck. Amplification or overexpression of HER2 occurs in approximately 15â30% of breast cancers and 10â30% of gastric/gastroesophageal cancers and serves as a prognostic and predictive biomarker. Dimerization of the receptor results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the receptors and initiates a variety of signaling pathways leading to cell proliferation and tumorigenesis. ![]() Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family having tyrosine kinase activity. ![]()
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