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      Gastric cancer: somatic genetics as a guide to therapy.

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          Abstract

          Gastric cancer is the leading cause of cancer-related mortality across the world, with poor prognosis and a median overall survival of ≤12 months for advanced stage gastric cancer. Environmental, genetic and other predisposing factors contribute to the development of gastric cancer and a predominant factor was found to be infection of Helicobacter pylori Advances in understanding the deranged signalling pathways that are critical for normal cellular homeostasis helped in the development of novel drugs that target specific proteins and pathways to curtail the growth of gastric cancer. Genetic studies revealed several single nucleotide polymorphisms, chromosomal aberrations and epigenetic alterations that likely play a major role in elevating the susceptibility to develop gastric cancer. Methylation pattern of specific genes may likely prove to be a valid biomarker for early detection of gastric cancer, but much progress is needed to establish specific markers. Important developments have been made in targeting human epidermal growth factor receptor-2 and vascular endothelial growth factor receptor 2 for treating advanced gastro-oesophageal junction cancer, using specific monoclonal antibodies. Lack of efficacy with regard to targeting other signalling pathways including mesenchymal-epithelial transition/hepatocyte growth factor and mammalian target of rapamycin is probably due to suboptimal patient selection for these clinical trials, which is probably due to the lack of appropriate biomarkers, to decide on responsive patient population. Besides the development of antagonists for the cell growth-related signalling pathways, advances are also being made to tackle gastric cancer by immunotherapies, targeting immune check-points, which may hold promise for better treatment options in future.

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          Author and article information

          Journal
          J. Med. Genet.
          Journal of medical genetics
          BMJ
          1468-6244
          0022-2593
          May 2017
          : 54
          : 5
          Affiliations
          [1 ] Nanjing University of Chinese Medicine, Information Institute, Nanjing, Jiangsu, China.
          [2 ] Xuzhou Central Hospital, Xuzhou, Jiangsu Province, China.
          [3 ] The Affiliated XuZhou Hospital of Medical College of Southeast University, Xuzhou, Jiangsu Province, China.
          [4 ] Xuzhou Clinical School of Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
          [5 ] Xuzhou Clinical Medical College of Nanjing University of Chinese Medicine, Xuzhou, Jiangsu Province, China.
          Article
          jmedgenet-2016-104171
          10.1136/jmedgenet-2016-104171
          27609016
          ed544047-4e65-417f-87aa-1e512a849d83
          History

          Cancer: gastric,Cancer: oesophageal,Epigenetics,Genetics,Stomach and duodenum

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