Inhibition of angiogenesis at endothelial cell level.

Targeting of proliferating endothelial cells may allow a new therapeutic strategy against malignant tumors. Endothelial cells are easily accessible through the blood stream and genetically stable, reducing the possibility of acquiring drug resistance. There are numerous candidates for angiogenesis targets of drug development, e.g. a single endothelial cell has 2,000-20,000 different receptors on a cell membrane and inside a cell there are hundreds of second messengers. Inhibitors that are active at endothelial cells can be placed in three main groups inducing blockage of endothelial cell activator, direct inhibition of endothelial cells, inhibition of endothelial specific signaling. This review summarizes different approaches already in clinical trials. Specific effort is taken to give a view of and a new perspective over clinically relevant basic mechanisms, e.g. VEGF, ETS and radionanotargeting. It is clear that aggressive development work both at the preclinical and clinical levels is still needed; however, breakthroughs in applied therapies are expected at any time. Copyright 2002 Wiley-Liss, Inc.