Sara Petrillo, Emanuela Tolosano, Luca Munaron and Tullio Genova* Pages 422 - 427 ( 6 )
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 and metastatisation.
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.
Angiogenesis inhibition, endothelial cell metabolism, tumor angiogenesis, vessel normalization.
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy; Address: via Nizza 52, Torino, Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy; Address: via Nizza 52, Torino, Department of Life Sciences and Systems Biology, University of Torino, Torino, Italy. Address: via Accademia Albertina 13, Torino, Department of Life Sciences and Systems Biology, University of Torino, Torino, Italy. Address: via Accademia Albertina 13, Torino