Targeted therapy in gastric cancer

APMIS. 2015 May;123(5):365-72. doi: 10.1111/apm.12359. Epub 2015 Feb 23.

Abstract

Gastric cancer is often diagnosed at an advanced stage. Although chemotherapy prolongs survival and improves quality of life, the survival of gastric cancer patients with advanced disease is short. Thanks to recent insights into the molecular pathways involved in gastric carcinogenesis, new targeted treatment options have become available for gastric cancer patients. Trastuzumab, an antibody targeted to HER-2, was shown to improve survival of advanced gastric cancer patients harboring HER-2 overexpression due to gene amplification in their tumor cells, and is currently also explored in adjuvant and neoadjuvant settings. Another agent with promising results in clinical trials is ramucirumab, an antibody targeting VEGFR-2. No clear survival benefit, however, were experienced with agents targeting EGFR (cetuximab, panitumumab), VEGF-A (bevacizumab), or mTOR (everolimus). Drugs targeting c-MET/HGF are currently under investigation in biomarker-selected cohorts, with promising results in early clinical trials. This review will summarize the current status of targeted treatment options in gastric cancer.

Keywords: Gastric cancer; HER-2; VEGFR-2; targeted therapy; trastuzumab.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Clinical Trials as Topic
  • ErbB Receptors / antagonists & inhibitors
  • Hepatocyte Growth Factor / antagonists & inhibitors
  • Humans
  • Molecular Targeted Therapy / methods*
  • Molecular Targeted Therapy / trends
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors
  • Ramucirumab
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / therapy*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Trastuzumab
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • HGF protein, human
  • Hepatocyte Growth Factor
  • MTOR protein, human
  • EGFR protein, human
  • ErbB Receptors
  • KDR protein, human
  • Proto-Oncogene Proteins c-met
  • Receptor, ErbB-2
  • Vascular Endothelial Growth Factor Receptor-2
  • TOR Serine-Threonine Kinases
  • Trastuzumab