Targeting angiogenesis: vascular endothelial growth factor and related signaling pathways

Angiogenesis is necessary for the development of epithelial ovarian cancer (EOC) by prompting tumor growth and supporting metastatic spread. Anti-angiogenesis agents have been studied extensively as frontline, maintenance and recurrent treatment in EOC. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), is the most widely studied of these agents and the first to be approved by the United States Food and Drug Administration for treatment of recurrent platinumresistant EOC. Recent clinical trials have also investigated VEGF independent pathways including fibroblast growth factor (FGF) receptors, platelet-derived growth factor (PDGF) receptors, angiopoietins, and the notch pathway. This review summarizes the clinical rationale, the mechanisms of action and clinical results for angiogenesis inhibitors under evaluation in Phase II and III trials for EOC. Anti-angiogenesis agents reviewed in this paper include aflibercept, bevacizumab, cediranib, fosbretabulin, nintedanib, pazopanib, sorafenib, trebananib, and vandetanib. Due to the costs and toxicities associated with anti-angiogenics, biomarker or molecular signature selection strategy for patients who will most benefit would be ideal, but no such strategy has been validated to date.