TUMOR VASCULATURE TARGETED THERAPIES - GETTING THE PLAYERS ORGANIZED

Based on their location and central role in solid tumor growth, tumor vascular endothelial cells may present an attractive target for the de livery of therapeutic drugs or cells. The potency of blocking the tumo r blood supply in eradicating solid tumors was demonstrated recently i n a mouse model of tumor vasculature targeting (Huang et al., Science 275: 547-550, 1997). For clinical application of such strategies, tumo r endothelium specific target epitopes need to be identified. Recent s tudies on angiogenesis have identified angiogenesis related molecules as potential target epitopes. Among these are vascular endothelial gro wth factor (VEGF)/VEGF-receptor complex, alpha v integrins, and Tie re ceptor tyrosine kinases. Besides blockade of their signalling cascades leading to inhibition of angiogenesis, these epitopes may also be ins trumental in tumor vessel specific delivery of therapeutics. Data on t he efficacy of therapeutic modalities aimed at these, mostly heterogen eously distributed tumor endothelial epitopes are scarce, and sophisti cated experimentation is required to rationalize the development of ne w therapeutic strategies. Importantly, only detailed evaluations in ca ncer patients will provide the blueprint for the development of clinic ally effective tumor vascular targeted therapies. BIOCHEM PHARMACOL 55 ;12:1939-1945, 1998. (C) 1998 Elsevier Science Inc.