Targeting endothelial cell metabolism in cancerous microenvironment: a new approach for anti-angiogenic therapy

Abstract

Anti-angiogenic therapy is a practical approach to managing diseases with increased angiogenesis, such as cancer, maculopathies, and retinopathies. Considering the fundamental gaps in the knowledge of the vital pathways involved in angiogenesis and its inhibition and the insufficient efficiency of existing angiogenesis inhibitors, there is an increasing focus on the emergence of new therapeutic strategies aimed at inhibiting pathological angiogenesis. Angiogenesis is forming a new vascular network from existing vessels; endothelial cells (ECs), vascular lining cells, are the main actors of angiogenesis in physiological or pathological conditions. Switching from a quiescent state to a highly migratory and proliferative state during new vessel formation called “angiogenic switch” is driven by a “metabolic switch” in ECs, angiogenic growth factors, and other signals. As the characteristics of ECs change by altering the surrounding environment, they appear to have a different metabolism in a tumor microenvironment (TME). Therefore, pathological angiogenesis can be inhibited by targeting metabolic pathways. In the current review, we aim to discuss the EC metabolic pathways under normal and TME conditions to verify the suitability of targeting them with novel therapies.

Keywords:

• Tumor microenvironment
• metabolism
• tumor endothelial cell
• angiogenesis inhibitors
• metabolic switch
• targeted therapies

Author contributions

The idea was from Parisa Mohammadi and Kamran Mansouri, the literature search was done by Parisa Mohammadi and Reza Yarani, and drafted by Fatemeh Ranjbarnejad, and Joana Mendes Lopes de Melo critically revised the work. Kamran Mansouri and Azam Rahimpour supervised all the steps. Then all authors read and approved the final manuscript.

Disclosure statement

The authors declare that there are no conflicts of interest.

Additional information

Funding

This research was funded by National Institute for Medical Research Development (NIMAD), grant number 973689.