title: Vessel pruning or healing: endothelial metabolism as a novel target?
abstract: Antiangiogenic drugs were originally designed to starve tumors by cutting off their vascular supply. Unfortunately, when these agents are used as monotherapy or in combination with chemotherapy, they provide only modest survival benefits in the order of weeks to months in most cancer patients. Strategies normalizing the disorganized tumor vasculature offer the potential to increase tumor perfusion and oxygenation, and to improve the efficacy of radio-, chemo- and immunotherapy, while reducing metastasis. Areas covered: This review discusses tumor vascular normalization (TVN) as an alternative strategy for anti-angiogenic cancer treatment. We summarize (pre)-clinical strategies that have been developed to normalize tumor vessels as well as their potential to enhance standard therapy. Notably, we describe how targeting endothelial cell metabolism offers new possibilities for antiangiogenic therapy through evoking TVN. Expert opinion: Several drugs targeting VEGF signaling are now clinically used for antiangiogenic cancer treatment. However, excessive blood vessel pruning impedes perfusion and causes tumor hypoxia, known to promote cancer cell dissemination and impair radio-, chemo- and immunotherapy. Normalized vessels lessen tumor hypoxia, impair cancer cell intravasation and enhance anticancer treatment. New data indicate that targeting endothelial cell metabolism is an alternative strategy of antiangiogenic cancer treatment via promotion of TVN.
authors.affiliation: a Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology , KU Leuven , Leuven , Belgium.|b Laboratory of Angiogenesis and Vascular Metabolism , Vesalius Research Center, Center for Cancer Biology (CCB), VIB , Leuven , Belgium.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Cantelmo
authors.affiliation: a Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology , KU Leuven , Leuven , Belgium.|b Laboratory of Angiogenesis and Vascular Metabolism , Vesalius Research Center, Center for Cancer Biology (CCB), VIB , Leuven , Belgium.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pircher
authors.affiliation: a Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology , KU Leuven , Leuven , Belgium.|b Laboratory of Angiogenesis and Vascular Metabolism , Vesalius Research Center, Center for Cancer Biology (CCB), VIB , Leuven , Belgium.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kalucka
authors.affiliation: a Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology , KU Leuven , Leuven , Belgium.|b Laboratory of Angiogenesis and Vascular Metabolism , Vesalius Research Center, Center for Cancer Biology (CCB), VIB , Leuven , Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; anti angiogenic therapy; endothelial cell metabolism; tumor vessel normalization