Combining Antiangiogenic Agents with Metronomic Chemotherapy Enhances Efficacy against Late-stage Pancreatic Islet Carcinomas in Mice

Angiogenesis, the formation of new blood vessels, isessential for most tumors to expand (Hanahan and Folkman 1996). Conversely, inhibition of this complex process can demonstrably restrict tumor growth and evenelicit tumor shrinkage or regression in animal models(Folkman 2000). Thus, it is not surprising thatwidespread efforts in industry and academia have focused on the generation of antiangiogenic drugs that target the endothelial cells, the structural constituents of thevascular system. Antiangiogenic therapy takes advantageof the fact that tumor endothelial cells are chronically activated to proliferate and migrate in the course of assembling a neovasculature, in contrast to the largely quiescent endothelium found in the vessels of normal organs.Most of the current angiogenesis inhibitors were identified by their ability to block proliferation or migration ofcultured tumor endothelial cells, typically resulting in endothelial cell apoptosis...