الفهرس 
Biology of HER2/neuOnly 14 pages are availabe for public view
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Abstract
Human epidermal growth factor receptor 2 (HER2) is overexpressed on the cell surface and there is gene amplification in approximately 20% of all breast cancers , gastric cancer , head and neck cancers . (Rahman., et al 2012).
HER2 is a member of the HER family of tyrosine kinase cell surface receptors, also called ErbB. They are named HER1/ErbB1 (or epidermal growth factor receptor [EGFR]), HER2/ErbB2, HER3/ErbB3, and HER4/ErbB4 A number of ligands have been identified that bind to HER1, HER3, and HER4, including EGF, transforming growth factor alpha (TGF-α), and the ”regulins” such as amphiregulin, epiregulin, and neuregulin. (Mouridsen et al., 2000).
HER2-mediated signaling is associated with cell proliferation, survival, and motility. In HER2-postive cells these growth signals are thought to be driven mainly through HER2/HER3 heterodimers. Because HER3 lacks an associated tyrosine kinase, it requires HER2 for signal transduction, which results in activation of the PI3K-AKT pathway HER2 homodimers activate the Ras-Raf pathway. ( Abrams et al. , 1999).
Two HER2-targeted therapies are currently available for the management of breast cancer: the immunoglobulin G1 (IgG1) antibody trastuzumab and the tyrosine kinase inhibitor lapatinib. (Lupa et al., 2010).
Trastuzumab binds to the extracellular HER2 receptor, where it disrupts HER2 signaling, downregulates HER2 expression, inhibits cell cycle progression, andinduces antibody-dependent cell-mediated cytotoxicity (ADCC). In addition, trastuzumab inhibits HER2 shedding which reduces levels of p95-HER2 . (Leitzel et al., 2008).
Lapatinib is a small-molecule inhibitor of the tyrosine kinase associated with HER2. It prevents phosphorylation and thereby inhibits downstream signaling. Lapatinib also inhibits the tyrosine kinase associated with HER1 (EGFR). ( Molina et al .,1996).
Despite the clinical benefits reported with HER2-targeted therapy, both de novo and acquired resistance to trastuzumab and lapatinib has been reported.(Yamauch et al , 1997).
Because of the importance of dimerization in the HER2 signaling cascade, a rational approach is to inhibit the dimerization of HER2, either as homo- or heterodimers. Pertuzumab is the first-in-class ”HER dimerization inhibitor. and is now FDA-approved for use with trastuzumab and chemotherapy for treatment-naïve, HER2-positive, metastatic breast cancer. (Hamliton et al ,2000).