Gene therapy strategies for tumor antiangiogenesis
Based on the concept that solid tumors cannot grow without the generation of new blood vessels, there is growing interest in the use of antiangiogenesis agents to inhibit tumor growth. This review summarizes the concepts of using gene transfer vectors to provide high concentration of antiangiogenic proteins within an organ. While there are many challenges that must be met before antiangiogenesis can be used to effectively treat human tumors, gene transfer strategies have the potential to provide sustained, high, local concentrations of antiangiogenic mediators specifically targeted to organs containing tumors, minimizing systemic toxicity. Antiangiogenesis gene therapy strategies will most likely be effective in a state of low tumor burden, where this "genetic tourniquet" can provide trans (i.e., acting in the extracellular milieu as opposed to within tumor cells) suppression of the growth of endothelial cells in the milieu of micrometastases.