title: Targeted therapy for gastric cancer: Current status and future directions (Review).
abstract: According to the 2012 statistics of the International Agency for Research on Cancer (IARC), gastric cancer is the fifth most common malignancy, and the third leading cause of cancer-related deaths worldwide. Conventional chemotherapy and radiation have shown limited efficacy for advanced gastric cancer, showing an overall survival (OS) rate of ~10 months. Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2), is the first approved molecularly targeted agent for HER2-overexpressing gastric cancer, which was found to prolong the OS and the progression-free survival (PFS) of patients. However, HER2 overexpression is present only in a minority of patients with gastric cancer. Hence, other targeted agents are urgently needed. Ramucirumab, a novel human IgG1 monoclonal antibody that selectively targets the extracellular domain of VEGF receptor 2 (VEGFR2), is regarded as a new standard second-line treatment for patients with advanced gastric cancer. The combination of two or more targeted agents directed against two different molecular targets may improve the survival of patients with advanced gastric cancer. Although great efforts have been made, the effect of targeted therapy for gastric cancer is limited. One key reason is that participants in clinical trials for new targeted agents were not selected by detection of the targeted molecule. Here, we review clinical trials related to molecular targets such as anti-epidermal growth factor receptor signaling including anti-HER2 and anti-EGFR1, anti-VEGF signaling, anti-mammalian target of rapamycin (mTOR), tyrosine kinase inhibitors (TKIs) and anti-MET.
authors.affiliation: Department of Internal Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Yuan
authors.affiliation: Department of Internal Oncology Ward 7, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong 250031, P.R. China.
authors.forename: Zhong-Xiu
authors.initials: ZX
authors.lastname: Zhu
authors.affiliation: Department of Internal Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Internal Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D006801:Humans; D058990:Molecular Targeted Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000068878:Trastuzumab / Q000627:therapeutic use; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000235:genetics*; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D040301:Vascular Endothelial Growth Factor Receptor-2; D000096662:Ramucirumab; C508053:ERBB2 protein, human; C000588866:KDR protein, human