title: Optimization of tumor radiotherapy with modulators of cell metabolism: toward clinical applications.
abstract: Most solid tumors are characterized by unstable perfusion patterns, creating regions of hypoxia that are detrimental to radiotherapy treatment response. Because postsurgical radiotherapy, alone or in combination with other interventions, is a first-line treatment for many malignancies, strategies aimed at homogeneously increasing tumor pO2 have been the focus of intense research over the past decades. Among other approaches of demonstrable clinical and preclinical utility, this review focuses on those directly targeting oxygen consumption to redirect oxygen from a metabolic fate to the stabilization of radiation-induced DNA damage, more particularly drugs targeting glucose and lactate metabolism, nitric oxide donors or inducers, and mitogen-activated protein kinase pathway inhibitors. Their utility as adjuvant treatments with radiotherapy has been proven preclinically, which should foster further their clinical development and evaluation.
authors.affiliation: Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute (LDRI), Université catholique de Louvain (UCL) Medical School, Brussels, Belgium; Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCL) Medical School, Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Danhier
authors.forename: Christophe J
authors.initials: CJ
authors.lastname: De Saedeleer
authors.forename: Oussama
authors.initials: O
authors.lastname: Karroum
authors.forename: Géraldine
authors.initials: G
authors.lastname: De Preter
authors.forename: Paolo E
authors.initials: PE
authors.lastname: Porporato
authors.forename: Bénédicte F
authors.initials: BF
authors.lastname: Jordan
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
authors.forename: Pierre
authors.initials: P
authors.lastname: Sonveaux
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000528:radiation effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000528:radiation effects; D006801:Humans; D007773:Lactates / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
chemical_list: D007773:Lactates; D011838:Radiation-Sensitizing Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose; D010100:Oxygen