Angiogenesis: New targets for the development of anticancer chemotherapies

Angiogenesis is the process by which new blood vessels are formed from pree xisting microvasculature. To ensure an adequate blood supply, tumor cells r elease angiogenic factors that are capable of promoting nearby blood vessel s to extend vascular branches to the tumor. In addition, larger rumors have been shown to release angiogeneic inhibitory factors that prevent blood ve ssels from sending branches to smaller, more distant tumors that compete fo r oxygen and nutrients. Angiogenesis is a complex multistep biochemical pro cess, and offers several potential molecular targets for non-cytotoxic anti cancer therapies. Strategies for exploiting tumor angiogenesis for novel ca ncer drug discovery include: (i) inhibition of proteolytic enzymes that bre akdown the extracellular matrix surrounding existing capillaries; (ii) inhi bition of endothelial cell migration; (iii) inhibition of endothelial cell proliferation; (iv) enhancement of tumor endothelial cell apoptosis. There is also a host of miscellaneous agents that inhibit angiogenesis for which the specific mechanisms are not clear. Several methods have been developed for measuring antiangiogenic activity both in vitro and in vivo. Although t here has been intensive research efforts focused at the phenomena of angiog enesis, as well as the search for antiangiogenic agents for more than two d ecades, many questions remain unanswered with regard to the overall biochem ical mechanisms of the angiogenesis process and the potential therapeutic u tility of angiogenic inhibitors. Nevertheless potent angiogenic inhibitors capable of blocking tumor growth have been discovered, and appear to have p otential for development into novel anticancer therapeutics. However there are still hurdles to be overcome before these inhibitors become mainstream therapies.