Gastric Carcinoma at the Era of Targeted Therapies

Curr Drug Targets. 2016;17(15):1818-1826. doi: 10.2174/1389450116666150506111327.

Abstract

Gastric and gastro-esophageal cancers (GC/GEJ) appear as the second cancer-related death worldwide. Diagnosis is made at an advanced stage offering a curative attempt in less than 50% of cases. Despite the improvements of the systemic cytotoxic chemotherapy regimens, the prognosis of patients with metastatic GC/GEJ cancer remains poor. Recent insights in biochemical pathways have permitted to identify potential targets. The extracellular domain of HER2 receptors is implicated in cells' proliferation and in the anti-apoptotic process occurring in GC/GEJ cancers. Trastuzumab, a monoclonal antibody targeting HER2, in addition to chemotherapy permitted to obtain more than one year of survival in HER2-positive advanced GC/GEJ cancers. Recently, ramucirumab, a humanized monoclonal antibody targeting VEGFR-2 receptor demonstrated its efficacy as a second line treatment for patients with advanced GC/GEJ cancer. These encouraging results have justified evaluating targeted therapies in GC/GEJ cancers. In this review, we summarize targeted therapies that might present clinical efficacy in the treatment of advanced GC/GEJ cancers.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / metabolism
  • Humans
  • Molecular Targeted Therapy / methods*
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / chemistry
  • Receptor, ErbB-2 / metabolism
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Trastuzumab / pharmacology
  • Trastuzumab / therapeutic use
  • Treatment Outcome
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • ramucirumab
  • ERBB2 protein, human
  • KDR protein, human
  • Receptor, ErbB-2
  • Vascular Endothelial Growth Factor Receptor-2
  • Trastuzumab