CONTEXT

Targeting tumor vasculature to disrupt existing tumor progression is a promising strategy because it aims only endothelial cells and it is therefore less damaging to surrounding healthy tissue. Moreover, endothelial cells "more stable" than the cancer cells are less susceptible to phenotypic and genotypic changes, and therefore the risk of developing resistance to treatment is minimized. The main representative of antivascular agents is the combretastatin A-4 (CA-4). It interacts with tubulin and leads to destabilization of the cytoskeleton of endothelial cells of intratumoral neovessels, leading to a detachment of the basement membrane and promotion of apoptosis. It is interesting to note that this agent is preferentially active on proliferating endothelial cells within tumor lesions but respects the endothelial cells of normal tissues.

To date, only two molecules targeting tumor vasculature have been the subject of a Phase III clinical study (fosbretabulin, ombrabuline), while the market for chemotherapy agents than a hundred of approved drugs in the treatment of cancer. Consequently, the market activity for antivascular agents is open to the arrival of new molecules with a novel mechanism of action.