title: New agents on the horizon in gastric cancer.
abstract: BACKGROUND
  Conventional cytotoxic chemotherapy has been the backbone of advanced gastric cancer treatment for decades and still represents a key element of the therapeutic armamentarium. However, only small increments in survival outcomes have been reached. A better understanding of genetic alterations and molecular signatures of gastric cancer has been reached in the last years. It will serve as a roadmap for better treatment stratification and future drug development.
  
  
  METHODS
  We reviewed preclinical and clinical studies that assessed novel treatment targets and emerging drug therapies in gastric cancer. We performed research via PubMed, and the congress webpages of the American Society of Clinical Oncology, European Society of Medical Oncology and the Japanese Society of Medical Oncology.
  
  
  RESULTS
  HER2-targeting with trastuzumab is effective in HER2-positive metastatic gastric cancer; combined HER2 targeting strategies are being investigated. Studies assessing the role of HER2 targeting in the perioperative setting are ongoing. Novel treatment targets include inhibition of cancer stemness-related signaling pathways like STAT3. DNA damage repair and Claudin 18.2, a tight junction protein with high expression in gastric cancers are also novel molecular drug targets. Modification of the tumor microenvironment, including activation of immune response by PD-1/PD-L1 checkpoint inhibitors and stroma modification by matrix metalloproteinase-9 inhibition, led to first promising treatment results.
  
  
  CONCLUSIONS
  Novel treatment options for gastric cancer patients are emerging. They involve novel mechanisms of action, and are based on our constantly increasing understanding of tumor biology and better molecular stratification of gastric cancer patients.
authors.affiliation: University Cancer Center Leipzig, University Medicine Leipzig, Leipzig, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Lordick
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shitara
authors.affiliation: Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, USA.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Janjigian
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D007167:Immunotherapy; D014411:Neoplastic Stem Cells / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy; D059016:Tumor Microenvironment
chemical_list: D020533:Angiogenesis Inhibitors; D000074322:Antineoplastic Agents, Immunological
keywords: Claudin 18.2; HER2; STAT3; gastric cancer; immunotherapy; stem cell inhibition