1. Targeting endothelial metabolism for anti-angiogenesis therapy: A pharmacological perspective.
- Author
-
Missiaen R, Morales-Rodriguez F, Eelen G, and Carmeliet P
- Subjects
- Animals, Endothelial Cells metabolism, Endothelial Cells pathology, Endothelium, Vascular metabolism, Endothelium, Vascular pathology, Endothelium, Vascular physiopathology, Humans, Intercellular Signaling Peptides and Proteins metabolism, Molecular Targeted Therapy, Signal Transduction drug effects, Angiogenesis Inhibitors pharmacology, Endothelial Cells drug effects, Endothelium, Vascular drug effects, Energy Metabolism drug effects, Neovascularization, Pathologic, Neovascularization, Physiologic drug effects
- Abstract
Current anti-angiogenic therapies in malignant and ocular diseases target growth factor signaling in order to attenuate excessive vascular growth. Although initial responses are promising, overall therapeutic success is limited due to insufficient efficiency, tumor refractoriness and resistance. Emerging evidence suggests that diverse growth factor signaling pathways in endothelial cells (ECs) converge onto cellular metabolism, creating an attractive target for novel alternative anti-angiogenic therapies. Recent studies show that ECs rely on glycolysis for ATP and biomass synthesis, necessary for proliferation and migration, key processes of angiogenesis. In addition, fatty acid β-oxidation (FAO) is essential for de novo nucleotide synthesis during EC proliferation. Initial proof-of-evidence has been given that administration of pharmacological inhibitors of those metabolic pathways can be used to inhibit pathological angiogenesis in vivo. Deciphering the role of other metabolic pathways and exploring the therapeutic potential of blocking these pathways await further investigation., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF