Anti-angiogenic therapy: concept to clinic.

It has been 40 years since Folkman hypothesized the use of anti-angiogenic therapy as a strategy in the treatment of cancer. Since then, vascular endothelial growth factor (VEGF) has been identified as the most potent cytokine to induce angiogenesis and drugs targeting VEGF, principally the humanized monoclonal antibody bevacizumab and the tyrosine kinase inhibitors sunitinib and sorafenib, have proven therapeutic benefit. The initial high expectations of tumor vascular targeting agents, however, have yet to be fulfilled. In unselected patient populations, the benefits of these agents is often marginal, they cause harmful side effects, and drug resistance is quickly established. Biomarkers to identify patients suitable for anti-angiogenic therapy will be key to the future development of these drugs.