title: c-Met targeting in advanced gastric cancer: An open challenge.
abstract: Despite significant improvements in systemic chemotherapy over the last two decades, the prognosis of patients with advanced gastric and gastroesophageal junction adenocarcinoma (GC) remains poor. Because of molecular heterogeneity, it is essential to classify tumors based on the underlying oncogenic pathways and to develop targeted therapies acting on individual tumors. High-quality research and advances in technology have contributed to the elucidation of molecular pathways underlying disease progression and have stimulated many clinical studies testing target therapies in an advanced disease setting. In particular, strong preclinical evidence for the aberrant activation of the HGF/c-Met signaling pathways in GC cancers exists. This review will cover the c-Met pathway, the mechanisms of c-Met activation and the different strategies of its inhibition. Next, we will focus on the current state of the art in the clinical evaluation of c-Met-targeted therapies and the description of ongoing randomized trials with the idea that in this disease, high quality translational research to identify and validate biomarkers is a priority task.
authors.affiliation: General, Minimally Invasive and Robotic Surgery, Department of Surgery, "San Matteo degli Infermi" Hospital, ASL Umbria 2, 06049 Spoleto, Italy. Electronic address: marano.luigi@email.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Marano
authors.affiliation: Department of Medical Oncology, "Santa Maria della Misericordia" Hospital, Azienda Ospedaliera di Perugia, 06132 Perugia, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Chiari
authors.affiliation: Division of Medical Oncology, Department of Clinical and Experimental Medicine "F. Magrassi-A. Lanzara", Second University of Naples, 80131 Naples, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Fabozzi
authors.affiliation: Division of Medical Oncology, Department of Clinical and Experimental Medicine "F. Magrassi-A. Lanzara", Second University of Naples, 80131 Naples, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: De Vita
authors.affiliation: Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, 06132 Perugia, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Boccardi
authors.affiliation: Department of Oncology, University of Siena, 53100 Siena, Italy.
authors.forename: Giandomenico
authors.initials: G
authors.lastname: Roviello
authors.affiliation: Department of Oncology, University of Siena, 53100 Siena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Petrioli
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Marrelli
authors.affiliation: Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Roviello
authors.affiliation: General, Minimally Invasive and Robotic Surgery, Department of Surgery, "San Matteo degli Infermi" Hospital, ASL Umbria 2, 06049 Spoleto, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Patriti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met
keywords: Advanced gastric cancer; Anti-c-Met drugs; Hepatocyte growth factor; Molecularly targeted agents; c-Met positive gastric cancer