Small-Molecule Vascular Disrupting Agents in Cancer Therapy

Abstract

SummaryIt is now widely accepted that for any tumor to grow to macroscopic size, a change to a proangiogenic phenotype leading to the formation of new blood vessels is required. This recognition has led to the development and clinical advancement of novel antiangiogenic therapeutics in cancer management. An alternative approach to targeting the neovasculature associated with tumors is not to interfere with new vessel formation but rather to disrupt the function of the tumor vasculature after it has already been formed. Vascular disrupting agents (VDAs) are designed to cause a rapid and selective vascular shutdown in tumors. The resulting ischemia produces rapid and extensive tumor cell kill. Treatment with VDAs has been shown to lead to extensive tumor necrosis in a wide variety of tumor models. VDAs also synergize with conventional anticancer treatments including radiotherapy and chemotherapy, and recent evidence indicates that VDA treatments are complimentary to antiangiogenic therapeutics. Lead VDAs have now entered clinical trials. This chapter focuses on the background and current state of development of VDAs and emphasizes their therapeutic potential when used in combination with conventional anticancer therapies and antiangiogenic agents.