title: Targeting endothelial metabolism for anti-angiogenesis therapy: A pharmacological perspective.
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.
authors.affiliation: Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, Leuven, Belgium.
authors.forename: Rindert
authors.initials: R
authors.lastname: Missiaen
authors.affiliation: Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, Leuven, Belgium.
authors.forename: Francisco
authors.initials: F
authors.lastname: Morales-Rodriguez
authors.affiliation: Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Eelen
authors.affiliation: Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, University of Leuven, Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, Leuven, Belgium. Electronic address: peter.carmeliet@vib-kuleuven.be.
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004734:Energy Metabolism / Q000187:drug effects*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D036341:Intercellular Signaling Peptides and Proteins