Vascular disrupting agents in cancer therapy

Abstract

Tumor blood vessel formation is a key process for tumor expansion. Tumor vessels are abnormal and differ from normal vessels in architecture and components. Besides oxygen and nutrients supply, the tumor vessels system, due to its abnormality, is responsible for: hypoxia formation, and metastatic routes. Tumor blood vessels can be a target of anti-cancer therapies. There are two types of therapies that target tumor vessels. The first one is the inhibition of the angiogenesis process. However, the inhibition is often ineffective because of alternative angiogenesis mechanism activation. The second type is a specific targeting of existing tumor blood vessels by vascular disruptive agents (VDAs). There are three groups of VDAs: microtubule destabilizing drugs, flavonoids with anti-vascular functions, and tumor vascular targeted drugs based on endothelial cell receptors. However, VDAs possess some limitations. They may be cardiotoxic and their application in therapy may leave viable residual, so called, rim cells on the edge of the tumor. However, it seems that a well-designed combination of VDAs with other anti-cancer drugs may bring a significant therapeutic effect. In this article, we describe three groups of vascular disruptive agents with their advantages and disadvantages. We mention VDAs clinical trials. Finally, we present the current possibilities of VDAs combination with other anti-cancer drugs.

Keywords: Anti-cancer therapy; Hypoxia; Tumor blood vessels; Vascular disrupting agents.