Combination Therapy with Chemotherapy and VDAs

Abstract

A growing body of preclinical and clinical evidence substantiates the feasibility of combining vascular disrupting agents (VDAs) and conventional anticancer therapies. The enhanced disease response to this combination is attributable to the respective activity of VDAs on the tumor vasculature and of the cytotoxic drug on proliferating tumor cells. However, the nature of the mode of action of VDAs is likely to cause pathophysiological modifications in the tumor microenvironment that can influence the delivery and the activity of the drug with which is combined. A full understanding of the action of VDAs, together with the pharmacological interactions with cytotoxic drugs, will expedite approaches aiming to maximize the antitumor effects of combination therapy. This review focuses on the rationales underpinning the combination of small molecule VDAs with chemotherapy, discussing the pathophysiological changes associated with VDA activity and implication of these for combination modalities.