Search results
Results from the WOW.Com Content Network
HER2 is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family. But contrary to other members of the ERBB family, HER2 does not directly bind ligand. HER2 activation results from heterodimerization with another ERBB member or by homodimerization when HER2 concentration are high, for instance in cancer. [8]
EGFR signaling cascades Diagram of the EGF receptor highlighting important domains. Epidermal growth factor receptor (EGFR) is a transmembrane protein that is activated by binding of its specific ligands, including epidermal growth factor and transforming growth factor alpha (TGF-α). [7]
There are 11 growth factors that activate ErbB receptors. The ability ('+') or inability ('-') of each growth factor to activate each of the ErbB receptors is shown in the table below: [15] A superposition of similar interfaces observed in crystal structures of the ERBB kinases, including EGFR, ERBB2 (HER2) and ERBB4 (HER4).
HER2 is an established therapeutic target within breast cancer, and the activation of HER2 is observed in approximately 20% of breast cancers as a result of overexpression. [ 19 ] [ 20 ] Trastuzumab , the first HER2-targeted drug developed in 1990, interferes with HER2 signalling.
With this mutation, cells are stimulated to divide by abnormally low levels of mitogens. One such example is HER2, a receptor tyrosine kinase that responds to the mitogen EGF. Overexpression of HER2 is common in 15-30% of breast cancers, [7] allowing the cell cycle to progress even with extremely low concentrations of EGF. The overexpression of ...
While no evidence has been found that ErbB3 overexpression, constitutive activation, or mutation alone is oncogenic, [18] the protein as a heterodimerization partner, most critically with ErbB2, is implicated in growth, proliferation, chemotherapeutic resistance, and the promotion of invasion and metastasis. [19] [20]
In HER2 overexpressing breast cancers, the HER2–IL-6–STAT3 signaling relationship could be targeted to develop new therapeutic strategies. [6] HER2 kinase inhibitors, such as lapatinib, have also demonstrated clinical efficacy in HER2 overexpressing breast cancers by disrupting a neuregulin-1 (NRG1)-mediated autocrine loop.
Trastuzumab binding to HER2 prevents homodimerization or heterodimerization (HER2/HER3) of the receptor, ultimately inhibiting the activation of MAPK and PI3K/AKT cellular signalling pathways. Because the monoclonal antibody targets HER2, and HER2 is only over-expressed in cancer cells, the conjugate delivers the cytotoxic agent DM1 ...