Vascular Endothelial Growth Factor A Inhibition in Gastric Cancer

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2015-01, Vol.18 (1), p.33-42
• Main Authors: Park, Do Joong, Thomas, Nicholas J., Yoon, Changhwan, Yoon, Sam S.
• Format: Article
• Language: English
• Subjects: Abdominal Surgery; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Animals; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents - therapeutic use; Bevacizumab; Cancer Research; Clinical Trials as Topic; Gastric cancer; Gastroenterology; Humans; Medicine; Medicine & Public Health; Molecular Targeted Therapy - methods; Neovascularization, Pathologic - drug therapy; Oncology; Prognosis; Ramucirumab; Receptors, Vascular Endothelial Growth Factor - immunology; Receptors, Vascular Endothelial Growth Factor - metabolism; Review Article; Signal Transduction - drug effects; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Surgical Oncology; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - physiology
• ISSN: 1436-3291; 1436-3305
• DOI: 10.1007/s10120-014-0397-4

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.