Novel angiogenesis inhibitors: addressing the issue of redundancy in the angiogenic signaling pathway.

Angiogenesis, the formation of new blood vessels from established vasculature, is a fundamental process in the growth and metastasis of solid tumours. It is a complex, tightly regulated process that requires the coordinated action of antiangiogenic and proangiogenic factors, the balance of which becomes disturbed during tumour development. Vascular endothelial growth factor (VEGF) and its receptor are the key mediators of angiogenesis and targets for multiple pharmacologic agents. Many patients treated with VEGF inhibitors survive for a longer period; however, eventual resistance is associated with progressive disease and death. Multiple approaches to overcome resistance have been investigated with varying success, including the use of agents that target multiple angiogenic factors or co-administration of angiogenesis inhibitors with standard chemotherapy or radiotherapy. It would appear that the future of angiogenic inhibitors lies in the intelligent combination of multiple targeted agents with other angiogenic inhibitors, as well as more conventional therapies to maximise therapeutic effect.