title: C-Met as a potential target for the treatment of gastrointestinal cancer: Current status and future perspectives.
abstract: Aberrant activation of the HGF/c-Met signalling pathways is shown to be related with cell proliferation, progression, metastasis, and worse prognosis in several tumor types, including gastrointestinal cancers, suggesting its value as a stimulating-target for cancer-therapy. Several approaches have been developed for targeting HGF and/or c-Met, and one of them, crizotinib (dual c-Met/ALK inhibitor), is recently been approved by FDA for lung-cancers with ALK-rearrangement. The main aim of current review is to give an overview on the role of c-Met/HGF pathway in gastrointestinal cancer, in preclinical and clinical trials. Although several important matters is still remained to be elucidated on the molecular pathways underlying the antitumor effects of this therapy in gastrointestinal-cancers. Further investigations are warranted to recognize the main determinants of the activity of c-Met inhibitors, for parallel targeting signalling pathway associated/activated via MET/HGF pathway or in response to the cell resistance to anti-c-Met agents. Additionally, identification of patients that might benefit from therapy could help to increase the selectivity and efficacy of the therapy.
authors.affiliation: Molecular Medicine Group, Department of Modern Sciences and Technology, Mashhad University of Medical Sciences, Mashhad, Iran.|Student Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Afsane
authors.initials: A
authors.lastname: Bahrami
authors.affiliation: Cancer Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Soodabeh
authors.initials: S
authors.lastname: Shahidsales
authors.affiliation: Neurogenic Inflammatory Research Center and Department of Physiology, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Khazaei
authors.affiliation: Metabolic syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Ghayour-Mobarhan
authors.affiliation: Metabolic syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mina
authors.initials: M
authors.lastname: Maftouh
authors.affiliation: Metabolic syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.|Department of Medical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyed Mahdi
authors.identifier: http://orcid.org/0000-0002-5247-4043
authors.initials: SM
authors.lastname: Hassanian
authors.affiliation: Metabolic syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Amir
authors.identifier: http://orcid.org/0000-0002-4968-0962
authors.initials: A
authors.lastname: Avan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004067:Digestive System Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C066855:HGF protein, human; D047428:Protein Kinase Inhibitors; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: c-Met inhibitors; c-Met/HGF pathway; resistance to targeted agents; upper gastrointestinal cancers