title: Personalizing therapies for gastric cancer: molecular mechanisms and novel targeted therapies.
abstract: Globally, gastric cancer is the 4(th) most frequently diagnosed cancer and the 2(nd) 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.
authors.affiliation: Michael Luis, António Araújo, Ramon Andrade de Mello, Gastrointestinal Unit, Service of Medical Oncology, Portuguese Oncology Institute, 4200-072 Porto, Portugal.
authors.forename: Michael
authors.initials: M
authors.lastname: Luis
authors.forename: Ana
authors.initials: A
authors.lastname: Tavares
authors.forename: Liliana S
authors.initials: LS
authors.lastname: Carvalho
authors.forename: Lúcio
authors.initials: L
authors.lastname: Lara-Santos
authors.forename: António
authors.initials: A
authors.lastname: Araújo
authors.forename: Ramon Andrade
authors.initials: RA
authors.lastname: de Mello
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D058990:Molecular Targeted Therapy; D018579:Patient Selection; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Afatinib; Biomarkers; Gastric cancer; Human epidermal growth factor receptor 2; Lapatinib; Pertuzumab; Target therapies; Trastuzumab; Trastuzumab-DM1