Targeting anionic phospholipids on tumor blood vessels and tumor cells.

摘要

Vascular targeting agents (VTAs) bind selectively to molecules that are present on tumor vasculature, and either recruit host effector cells or deliver agents that occlude or destroy tumor blood vessels [1]. This leads to an avalanche of tumor cell death through deprivation of oxygen and nutrients. VTAs have a number of advantages over other cancer therapies. First, a single vessel provides the nutrition and waste removal for hundreds or thousands of tumor cells, and only has to be damaged at a single point to block blood flow upstream and downstream. Second, the endothelial cell is in contact with the blood stream ensuring rapid drug delivery. Third, the target is unlikely to acquire genetic mutations that render it drug resistant. Fourth, VTAs act on existing as well as newly forming tumor vasculature. Finally, VTAs preferentially kill the hypoxic core regions of tumors, where the vasculature is most stressed and compromised, thus providing a complementary pattern of killing to chemotherapeutic drugs and irradiation, which are most effective against well-oxygenated peripheral regions of tumors.