Therapeutic approaches of angiogenesis inhibition: are we tackling the problem at the right level?

A growing body of evidence now demonstrates that inhibition of angiogenesis is a promising way for treatment of disease. Although the field of angiogenesis research is strongly linked to cancer biology, many other diseases were found to be dependent on angiogenesis as well, introducing a potential benefit from antiangiogenesis treatment. Recently, the first specific angiogenesis inhibitor was approved by the Food and Drug Administration for the treatment of colorectal cancer. Currently, several compounds with angiostatic activity are approved, and many are in late-stage clinical development. Most of these are indirect inhibitors, either clearing angiogenic growth factors from the circulation or blocking the signaling pathways activated by these growth factors. Although these compounds seem to represent an efficient strategy in cancer treatment, they possess an intrinsic threat to induce resistance. Therefore, it remains to be seen whether this strategy will be the most attractive in the future. Advancing insights into fundamental mechanisms will be necessary in the development of novel anticancer strategies based on inhibition of angiogenesis.