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Personalizing therapies for gastric cancer: Molecular mechanisms and novel targeted therapies
Authors:Michael Luis  Ana Tavares  Liliana S Carvalho  Lúcio Lara-Santos  António Araújo  Ramon Andrade de Mello
Affiliation:[1]Gastrointestinal Unit,Service of Medical Oncology,Portuguese Oncology Institute,4200-072 Porto,Portugal; [2]Gastrointestinal Unit,Experimental Pathology and Therapeutics Group,Research Center-Portuguese Oncology Institute,4200-072 Porto,Portugal; [3]Department of Pharmacology and Therapeutics,Faculty of Medicine,University of Porto,4200-319 Porto,Portugal; [4]Institute of Cellular and Molecular Biology,4150-180 Porto,Portugal; [5]Gastrointestinal Unit,Section of Surgical Oncology,Portuguese Oncology Institute,4200-072 Porto,Portugal; [6]Department of Medicine,Faculty of Medicine,University of Porto,4200-319 Porto,Portugal
Abstract:
Globally, gastric cancer is the 4th most frequently diagnosed cancer and the 2nd leading cause of death from cancer, with an estimated 990000 new cases and 738000 deaths registered in 2008. In the advanced setting, standard chemotherapies protocols acquired an important role since last decades in prolong survival. Moreover, recent advances in molecular therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2 (HER2) therapies. Trastuzumab, an anti-HER2 monoclonal antibody, was the first target drug in the metastatic setting that showed benefit in overall survival when in association with platinum-5-fluorouracil based chemotherapy. Further, HER2 overexpression analysis acquired a main role in predict response for trastuzumab in this field. Thus, we conducted a review that will discuss the main points concerning trastuzumab and HER2 in gastric cancer, providing a comprehensive overview of molecular mechanisms and novel trials involved.
Keywords:Gastric cancer   Human epidermal growth factor receptor 2   Biomarkers   Target therapies   Trastuzumab   Lapatinib   Pertuzumab   Trastuzumab-DM1   Afatinib
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