The VEGF pathway in cancer and disease: responses, resistance, and the path forward.

Antiangiogenesis was proposed as a novel target for the treatment of cancer 40 years ago. Since the original hypothesis put forward by Judah Folkman in 1971, factors that mediate angiogenesis, their cellular targets, many of the pathways they signal, and inhibitors of the cytokines and receptors have been identified. Vascular endothelial growth factor (VEGF) is the most prominent among the angiogenic cytokines and is believed to play a central role in the process of neovascularization, both in cancer as well as other inflammatory diseases. This article reviews the biology of VEGF and its receptors, the use of anti-VEGF approaches in clinical disease, the toxicity of these therapies, and the resistance mechanisms that have limited the activity of these agents when used as monotherapy.