Targeting Metabolism to Counteract Tumor Angiogenesis: A Review of Patent Literature

Massive vessel recruitment is required to sustain rapid tumor growth by delivering oxygen and nutrients. Current strategies to counteract angiogenesis are mostly aimed at reducing tumor vessel density. However, many of these drugs have been shown to trigger hypoxia, thus exacerbating tumor aggressiveness. Promising results come from a completely different approach based on the "normalization" of the endothelial layer and the consequent improvement of the vascular function. Since endothelial metabolism has proved essential in the regulation of the angiogenic switch, many recent patents focus on agents able to inhibit specific metabolic pathways in tumor-associated endothelial cells (TECs) in order to provide vessel normalization. This new strategy would ameliorate drug delivery to the tumor meanwhile reducing invasiveness and metastatisation. These findings might have important implication in clinics and could be particularly relevant to patients developing resistance to traditional anti-angiogenic drugs.