Targeting vascular endothelial growth factor (VEGF) pathway in gastric cancer: Preclinical and clinical aspects

• Gastric cancer (GC) is one of the most common causes of cancer-related deaths worldwide.
• Many VEGF-targeted agents were clinically tested in GC and they showed modest activity with considerable toxicity.
• Preclinical as well as clinical ramucirumab data in GC provide a new hope in that direction.
• The use of biomarkers to select GC patients for VEGF-targeted therapy should be considered for further clinical evaluation.

The prognosis of advanced gastric cancer has been dreadful with the majority of patients dying of their disease within 1 year of the diagnosis. In the advanced stage several therapeutic options can be discussed, including molecular targeted agents, but biological predicting factors are lacking. A number of molecular targets have been studied over the last decade bringing to several phase II studies; however very few agents moved into phase III clinical trials. The VEGFR-2 inhibitor monoclonal antibody ramucirumab has been recently approved in advanced progressing gastric cancer. This article reviews the basic science as well as clinical data of VEGF signaling in advanced gastric cancer with special emphasis on the different VEGF targeting agents tested previously in this disease.