Personalizing therapies for gastric cancer: molecular mechanisms and novel targeted therapies

World J Gastroenterol. 2013 Oct 14;19(38):6383-97. doi: 10.3748/wjg.v19.i38.6383.

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.

Keywords: Afatinib; Biomarkers; Gastric cancer; Human epidermal growth factor receptor 2; Lapatinib; Pertuzumab; Target therapies; Trastuzumab; Trastuzumab-DM1.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Molecular Targeted Therapy
  • Patient Selection
  • Precision Medicine*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Signal Transduction / drug effects
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / genetics
  • Trastuzumab
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab