title: Role of c-mesenchymal-epithelial transition pathway in gastric cancer.
abstract: BACKGROUND
  Gastric cancer is the fourth most common cancer burden worldwide; many patients show incurable disease at the time of diagnosis and prognosis remains unfavorable. Recently, new findings on gastric cancer biology led to the preclinical and clinical development of new compounds aiming to improve the overall survival and to preserve quality of life and reducing chemotherapy-related toxicities. Patients with human epidermal growth factor receptor 2 (HER2) overexpression/amplification have experienced benefit from the integration of trastuzumab to the standard chemotherapy. Ramucirumab has been recently approved in second line for treatment of gastric cancer.
  
  
  METHODS
  Drugs targeting molecules such as anti c-mesenchymal-epithelial transition (MET), mammalian target of rapamycin inhibitors, polo-like kinase 1 inhibitors are under investigation or in preclinical or early clinical development. Approximately 10 - 20% of gastric cancer presented an increased MET gene copy numbers; inappropriate activation of MET promotes cellular proliferation, cell motility, invasiveness and angiogenesis and is associated with more aggressive phenotype and with a lower survival.
  
  
  CONCLUSIONS
  The role of c-MET has been extensively evaluated both in Asian and Western population, even if data are far from being conclusive. The activation of MET/hepatocyte growth factor pathway is a negative prognostic factor, and it could partially explain the resistance to EGFR/HER2 inhibitors acting as a rescue pathway likewise in other tumors.
authors.affiliation: University Campus Bio-Medico Rome - Medical Oncology, via Alvaro del Portillo , 200, 00128, Rome , Italy e.dellaquila@unicampus.it.
authors.forename: Iacopo
authors.initials: I
authors.lastname: Fioroni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Dell'Aquila
authors.forename: Francesco
authors.initials: F
authors.lastname: Pantano
authors.forename: Salvatore
authors.initials: S
authors.lastname: Intagliata
authors.forename: Marco
authors.initials: M
authors.lastname: Caricato
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Roberto
authors.initials: R
authors.lastname: Coppola
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: c-mesenchymal–epithelial transition inhibitor; c-mesenchymal–epithelial transition pathway; gastric cancer; molecular targeted agents