Angiogenesis and angiogenesis inhibitors in cancer

Angiogenesis, the development of a new blood supply, is an essential process of tumour growth and metastasis. Over the past few years, this has led to the consideration of the tumour vasculature as an optimal target for anti-cancer strategies. The process of angiogenesis consists of a series of interactive events: quiescent endothelial cells are stimulated by angiogenic factors to degrade the underlying basement membrane, to migrate within the interstitial matrix, to proliferate and to organise themselves into tubular structures which become mature blood vessels. During angiogenesis, the endothelial cells undergo functional changes and show molecular features which are different from normal, quiescent endothelium. These differences can be exploited in order to selectively target tumour endothelium and to prevent neo-vessel formation. Two main approaches have been followed: i. the inhibition of the angiogenic process and vessel formation (anti-angiogenesis), and ii. direct targeting and destruction of tumour vasculature (vascular targeting). Compounds of different origin and mechanism of action have the potential to inhibit angiogenesis and hence tumour growth. This review takes into consideration some angiogenesis antagonists that are in development and the leader compounds that are under clinical trial for the treatment of cancer.