title: Manipulation of tumor oxygenation and radiosensitivity through modification of cell respiration. A critical review of approaches and imaging biomarkers for therapeutic guidance.
abstract: Tumor hypoxia has long been considered as a detrimental factor for the response to irradiation. In order to improve the sensitivity of tumors cells to radiation therapy, tumor hypoxia may theoretically be alleviated by increasing the oxygen delivery or by decreasing the oxygen consumption by tumor cells. Mathematical modelling suggested that decreasing the oxygen consumption should be more efficient than increasing oxygen delivery in order to alleviate tumor hypoxia. In this paper, we review several promising strategies targeting the mitochondrial respiration for which alleviation of tumor hypoxia and increase in sensitivity to irradiation have been demonstrated. Because the translation of these approaches into the clinical arena requires the use of pharmacodynamics biomarkers able to identify shift in oxygen consumption and tumor oxygenation, we also discuss the relative merits of imaging biomarkers (Positron Emission Tomography and Magnetic Resonance) that may be used for therapeutic guidance. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.
authors.affiliation: Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Université catholique de Louvain, Avenue Mounier 73.08, B-1200 Brussels, Belgium. Electronic address: bernard.gallez@uclouvain.be.
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
authors.affiliation: Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Université catholique de Louvain, Avenue Mounier 73.08, B-1200 Brussels, Belgium.
authors.forename: Marie-Aline
authors.initials: MA
authors.lastname: Neveu
authors.affiliation: Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Université catholique de Louvain, Avenue Mounier 73.08, B-1200 Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Danhier
authors.affiliation: Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Université catholique de Louvain, Avenue Mounier 73.08, B-1200 Brussels, Belgium.
authors.forename: Bénédicte F
authors.initials: BF
authors.lastname: Jordan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D015687:Cell Hypoxia / Q000187:drug effects; D003131:Combined Modality Therapy; D006801:Humans; D006931:Hyperbaric Oxygenation; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D010100:Oxygen / Q000494:pharmacology / Q000627:therapeutic use; D010101:Oxygen Consumption / Q000187:drug effects*; D011836:Radiation Tolerance / Q000187:drug effects*; D059016:Tumor Microenvironment; D014475:Uncoupling Agents / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D014475:Uncoupling Agents; D010100:Oxygen
keywords: Biomarkers; Imaging; Oxygen consumption; Radiotherapy; Tumor hypoxia; Tumor metabolism