Vascular Endothelial Growth Factor A Inhibition in Gastric Cancer

Angiogenesis is a vital process in the progression and metastasis of solids tumors including gastric adenocarcinoma. Tumors induce angiogenesis by secreting proangiogenic molecules such as vascular endothelial growth factor A (VEGF-A), and VEGF-A inhibition has become a common therapeutic strategy for many cancers. Several drugs targeting the VEGF-A pathway have been approved for clinical use in selected solid tumors, and several anti-VEGF-A strategies have been examined for gastric cancer. Phase II studies suggested that bevacizumab, an anti-VEGF antibody, can increase the efficacy of chemotherapy for advanced gastric cancer, but two international phase III trials failed to show an overall survival benefit. Two more recent international phase III trials have examined ramucirumab, an antibody targeting the primary receptor for VEGF-A, as second-line therapy for advanced gastric cancer and found a survival benefit both as single agent therapy and when combined with chemotherapy. Finally, correlative science studies suggest that the VEGF-A pathway may have varying importance in gastric cancer progression depending on ethnicity or race. This article will review the preclinical and clinical studies on the role of the VEGF-A pathway inhibition in gastric cancer.