Target molecules for anti-angiogenic therapy: from basic research to clinical trials

There is growing evidence that anti-angiogenic drugs will improve future th erapies of diseases like cancer, rheumatoid arthritis and ocular neovascula risation. However: it is still uncertain which kind of substance, out of th e large number of angiogenesis inhibitors, will prove to be a suitable agen t to treat these human diseases. There are currently more than 30 angiogene sis inhibitors in clinical trials and a multitude of promising new candidat es are under investigation in vitro and in animal models. Important therape utic strategies are: suppression of activity of the major angiogenic regula tors like vascular endothelial growth factor (VEGF) and fibroblast growth f actor (FGF); inhibition of function of alpha v-integrins and matrix metallo proteinases (MMPs); the exploitation of endogenous anti-angiogenic molecule s like angiostatin, endostatin or thrombospondin. Given the wide spectrum o f diseases which could be treated by anti-angiogenic compounds, it Is impor tant for today's clinicians to understand their essential mode of action at a cellular and molecular level. Here we give an in-depth overview of the b asic pathophysiological mechanisms underlying the different anti-angiogenic approaches used to date based on the most recent fundamental and clinical research data. The angiogenesis inhibitors in clinical trials are presented and promising future drug candidates are discussed. (C) 2000 Elsevier Scie nce Ireland Ltd. All rights reserved.