Angiogenic inhibitors in gastric cancers and gastroesophageal junction carcinomas: A critical insight

Crit Rev Oncol Hematol. 2015 Aug;95(2):165-78. doi: 10.1016/j.critrevonc.2015.02.009. Epub 2015 Mar 5.

Abstract

Advanced gastric cancer ranks second as the global leading cause of cancer-related death and improvements in systemic chemotherapy have reached a plateau. Advanced molecular sequencing techniques help identifying patients more likely to respond to targeted agents; nevertheless we are still far from major breakthroughs. Although antiangiogenic drugs have produced notable advances, redundant pathways or mechanisms of resistance may limit their efficacy. Novel compounds have been recently developed to specifically target VEGF receptors, PlGF, FGF, MET, and angiopoietin. Ramucirumab, a monoclonal antibody specifically directed against the VEGFR-2, has emerged as a novel therapeutic opportunity. REGARD and RAINBOW were the first phase III studies to report the value of this strategy in gastric cancer patients, and other ongoing trials are testing novel antiangiogenic compounds. The aim of our review is to present the state-of-the-art of novel antiangiogenic compounds in advanced gastric cancer, underlying the biology, their mechanism of action, and their clinical results.

Keywords: Advanced gastric cancer; Angiogenesis; Bevacizumab; Ramucirumab.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Carcinoma / blood supply
  • Carcinoma / drug therapy*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Esophageal Neoplasms / blood supply
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Humans
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / metabolism
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors
  • Proto-Oncogene Proteins c-met / metabolism
  • Ramucirumab
  • Stomach Neoplasms / blood supply
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Membrane Proteins
  • PIGF protein, human
  • KDR protein, human
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Vascular Endothelial Growth Factor Receptor-2