Mechanisms and future directions for angiogenesis-based cancer therapies.

Targeting angiogenesis represents a new strategy for the development of anticancer therapies. New targets derived from proliferating endothelial cells may be useful in developing anticancer drugs that prolong or stabilize the progression of tumors with minimal systemic toxicities. These drugs may also be used as novel imaging and radiommunotherapeutic agents in cancer therapy. In this review, the mechanisms and control of angiogenesis are discussed. Genetic and proteomic approaches to defining new potential targets on tumor vasculature are then summarized, followed by discussion of possible antiangiogenic treatments that may be derived from these targets and current clinical trials. Such strategies involve the use of endogenous antiangiogenic agents, chemotherapy, gene therapy, antiangiogenic radioligands, immunotherapy, and endothelial cell-based therapies. The potential biologic end points, toxicities, and resistance mechanisms to antiangiogenic agents must be considered as these therapies enter clinical trials.