Role of c-mesenchymal-epithelial transition pathway in gastric cancer

Introduction: Gastric cancer is the fourth most common cancer burdenworldwide; many patients show incurable disease at the time of diagnosisand prognosis remains unfavorable. Recently, new findings on gastric cancerbiology led to the preclinical and clinical development of new compoundsaiming to improve the overall survival and to preserve quality of life andreducing chemotherapy-related toxicities. Patients with human epidermalgrowth factor receptor 2 (HER2) overexpression/amplification have experiencedbenefit from the integration of trastuzumab to the standard chemotherapy.Ramucirumab has been recently approved in second line fortreatment of gastric cancer.Areas covered: Drugs targeting molecules such as anti c-mesenchymal-epithelialtransition (MET), mammalian target of rapamycin inhibitors, polo-likekinase 1 inhibitors are under investigation or in preclinical or early clinicaldevelopment. Approximately 10 -- 20% of gastric cancer presented anincreased MET gene copy numbers; inappropriate activation of MET promotescellular proliferation, cell motility, invasiveness and angiogenesis and isassociated with more aggressive phenotype and with a lower survival.Expert opinion: The role of c-MET has been extensively evaluated both inAsian and Western population, even if data are far from being conclusive.The activation of MET/hepatocyte growth factor pathway is a negativeprognostic factor, and it could partially explain the resistance to EGFR/HER2 inhibitors acting as a rescue pathway likewise in other tumors.