Tumor vasculature as target for therapeutic intervention

Solid tumors rely on efficient oxygen and nutrients transport for their growth, development and survival. Many tumors can stimulate new blood vessel formation. Because this angiogenic vasculature is aberrant from normal host vasculature, several strategies have been explored that specifically target tumor blood vessels.

Over the past decade, many molecules that act on tumor vasculature have been identified. They can be divided into three groups based on their mechanism of action: i) antiangiogenic molecules cause tumor growth arrest; ii) vasoactive agents induce hyperabnormalization of the tumor vasculature, improving conventional drug accumulation in the tumor; iii) vascular disrupting agents that cause blood vessel congestion, resulting in massive secondary tumor cell necrosis. Many investigational drugs from these classes are currently being evaluated to assess their role in tumor therapy.

The underlying principle of each of the strategies is discussed, and the (pre)clinical results of the investigational drugs in this class are highlighted.

To fully exploit the therapeutic potential of these drugs, it appears necessary to combine them with conventional anticancer agents, improve their selectivity for tumor vasculature, and develop biomarkers that predict the tumor sensitivity for these vascular strategies.