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• W2044179984 abstract "Emerging molecular targets in oncology: clinical potential of MET/hepatocyte growth-factor inhibitors Elizabeth C Smyth, Francesco Sclafani, David Cunningham Department of Gastrointestinal Oncology, Royal Marsden Hospital, Sutton, UK Abstract: The MET/hepatocyte growth-factor (HGF) signaling pathway plays a key role in the processes of embryogenesis, wound healing, and organ regeneration. Aberrant activation of MET/HGF occurs through multiple mechanisms including gene amplification, mutation, protein overexpression, and abnormal gene splicing interrupting autocrine and paracrine regulatory feedback mechanisms. In many cancers including non-small-cell lung cancer, colorectal, gastric, renal, and hepatocellular cancer, dysregulation of MET may lead to a more aggressive cancer phenotype and may be a negative prognostic indicator. Successful therapeutic targeting of the MET/HGF pathway has been achieved using monoclonal antibodies against the MET receptor and its ligand HGF in addition to MET-specific and multitargeted small-molecule tyrosine-kinase inhibitors with several drugs in late-phase clinical trials including onartuzumab, rilotumumab, tivantinib, and cabozantinib. MET frequently interacts with other key oncogenic tyrosine kinases including epidermal growth-factor receptor (EGFR) and HER-3 and these interactions may be responsible for resistance to anti-EGFR therapies. Similarly, resistance to MET inhibition may be mediated through EGFR activation, or alternatively by increasing levels of MET amplification or acquisition of novel “gatekeeper” mutations. In order to optimize development of effective inhibitors of the MET/HGF pathway clinical trials must be enriched for patients with demonstrable MET-pathway dysregulation for which robustly standardized and validated assays are required. Keywords: MET, HGF, colorectal cancer, gastric cancer, NSCLC, renal cancer, hepatocellular cancer, onartuzumab, rilotumumab, cabozantinib" @default.
• W2044179984 created "2016-06-24" @default.
• W2044179984 creator A5056345420 @default.
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• W2044179984 creator A5081006934 @default.
• W2044179984 date "2014-06-01" @default.
• W2044179984 modified "2023-09-25" @default.
• W2044179984 title "Emerging molecular targets in oncology: clinical potential of MET/hepatocyte growth-factor inhibitors" @default.
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