title: Gastric Cancer: New Drugs - New Strategies.
abstract: BACKGROUND
  Gastric cancer is the second most common cause of cancer-related deaths worldwide. There are large geographic variations in the incidence of these tumors, with 60% occurring in East Asia. For patients with resectable disease, surgery and perioperative treatment can be effective. For patients with advanced gastric cancer, chemotherapy regimens result in a median survival of 9-11 months. In general, the prognosis for advanced disease is poor and 5-year overall survival rates are around 15%. Combination therapies yield better survival rates, albeit with increased toxicity. Therefore, more effective and less toxic treatment regimens are needed.
  
  
  CONCLUSIONS
  The molecular aberrations that characterize the different subgroups of gastric cancer have been used as therapeutic targets. However, the heterogeneity and complexity of gastric cancers is a major challenge for the development of effective targeted therapies. This review examines the main molecular targets in the treatment of gastric cancer, namely the vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor (HGF)/c-Met, epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K)/Akt pathways.
  
  
  CONCLUSIONS
  The molecular aberrations characteristic of gastric cancer are being explored for the development of targeted therapies, including the VEGF, HER2, HGF/c-Met, EGFR and PI3K/Akt signaling pathways.
  
  
  CONCLUSIONS
  Trastuzumab, an antibody which targets HER2, is the first approved targeted therapy for the treatment of gastric cancer. However, trastuzumab is only effective in HER2-positive tumors (about 10-20% of all gastric cancers). Ramucirumab, which targets the VEGF receptor 2, has yielded benefits with respect to overall survival in a phase III trial and is an effective treatment for advanced gastric cancer with approval in second-line treatment. Apatinib and rilotumumab are another two promising new agents currently under development.
authors.affiliation: Department of Medicine II, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Nadin
authors.initials: N
authors.lastname: Schulte
authors.affiliation: Department of Medicine II, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Ebert
authors.affiliation: Department of Medicine II, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Härtel
keywords: Epidermal growth factor pathway; Gastric cancer; Human epidermal growth factor receptor 2 protein; Molecular targeting therapy; Vascular endothelial growth factors/vascular endothelial growth factor receptor pathway; c-Met inhibitors