Background: 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. This new strategy would ameliorate drug delivery to the tumor meanwhile reducing invasiveness
Objective: 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. Here, we provide a
review of the recent advances in the development of patents on agents targeting endothelial metabolism
that have proved effective in several vascular disorders.
Methods: Results of genetic and pharmacologic studies that brought to the development of patents for
methods to counteract aberrant angiogenesis were analysed and sub-divided according to the specific
metabolic pathway targeted.
Results: Growing evidences indicate that targeting specific molecular players involved in the endothelial
metabolic remodelling required to sustain aberrant angiogenesis, is a valuable therapeutic strategy
that can be exploited in vascular disorders as well as in tumor angiogenesis.
Conclusion: These findings might have important implications in clinics and could be particularly
relevant to patients developing resistance to traditional anti-angiogenic drugs.