title: Thirty years of research on met receptor to move a biomarker from bench to bedside.
abstract: Met receptor tyrosine kinase was discovered in 1984 as an oncogene. Thirty years later, Met and its ligand hepatocyte growth factor/scatter factor are promising targets for the novel therapies developed to fight against cancers, with more than 240 clinical trials currently conducted. In this review, we offer to trace and highlight the most recent findings of the exemplary track record of research on Met receptor, which allowed moving this biomarker from bench to bedside. Indeed, three decades of basic research unravelled the structural basis of the ligand/receptor interaction and their complex downstream signaling network. During this period, animal models highlighted their crucial role in the development and homeostasis of epithelial organs. In parallel, involvement of Met in tumorigenesis was confirmed by the direct association of its deregulation to poor prognosis in numerous cancers. On the basis of these data, pharmaceutical companies developed many Met inhibitors, some of which are in phase III clinical trials. These impressive achievements should not detract from many questions that still remain, such as the precise Met signaling involvement in development or homeostasis of specific epithelial structures. In addition, the processes involving Met in resistance to current therapies or the appearance of resistances to Met-targeted therapies are far from being fully understood.
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, Institut Pasteur de Lille, Université de Lille 1, Université de Lille 2, Lille, France.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Furlan
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, Institut Pasteur de Lille, Université de Lille 1, Université de Lille 2, Lille, France.
authors.forename: Zoulika
authors.initials: Z
authors.lastname: Kherrouche
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, Institut Pasteur de Lille, Université de Lille 1, Université de Lille 2, Lille, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Montagne
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, Institut Pasteur de Lille, Université de Lille 1, Université de Lille 2, Lille, France. Institut de Pathologie, CHR-U de Lille, Université de Lille 2, Lille, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Copin
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, Institut Pasteur de Lille, Université de Lille 1, Université de Lille 2, Lille, France.
authors.forename: David
authors.initials: D
authors.lastname: Tulasne
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism*; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / 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; D015415:Biomarkers; D008024:Ligands; D047428:Protein Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met