title: The meaning, measurement and modification of hypoxia in the laboratory and the clinic.
abstract: Hypoxia was identified as a microenvironmental component of solid tumours over 60 years ago and was immediately recognised as a potential barrier to therapy through the reliance of radiotherapy on oxygen to elicit maximal cytotoxicity. Over the last two decades both clinical and experimental studies have markedly enhanced our understanding of how hypoxia influences cellular behaviour and therapy response. Furthermore, they have confirmed early assumptions that low oxygenation status in tumours is an exploitable target in cancer therapy. Generally such approaches will be more beneficial to patients with hypoxic tumours, necessitating the use of biomarkers that reflect oxygenation status. Tissue biomarkers have shown utility in many studies. Further significant advances have been made in the non-invasive measurement of tumour hypoxia with positron emission tomography, magnetic resonance imaging and other imaging modalities. Here, we describe the complexities of defining and measuring tumour hypoxia and highlight the therapeutic approaches to combat it.
authors.affiliation: The Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Oxford, UK.
authors.forename: E M
authors.initials: EM
authors.lastname: Hammond
authors.affiliation: Wolfson Molecular Imaging Centre, Manchester, UK.
authors.forename: M-C
authors.initials: MC
authors.lastname: Asselin
authors.affiliation: Wolfson Molecular Imaging Centre, Manchester, UK.
authors.forename: D
authors.initials: D
authors.lastname: Forster
authors.affiliation: Centre for Imaging Sciences, Institute of Population Health, Manchester, UK.
authors.forename: J P B
authors.initials: JP
authors.lastname: O'Connor
authors.affiliation: The Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Oxford, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Senra
authors.affiliation: Manchester Pharmacy School, Cambridge-Manchester Cancer Research UK Comprehensive Imaging Centre, Manchester Academic Health Sciences Centre, The University Manchester, Manchester, UK. Electronic address: kaye.williams@manchester.ac.uk.
authors.forename: K J
authors.initials: KJ
authors.lastname: Williams
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015687:Cell Hypoxia; D004260:DNA Repair / Q000187:drug effects / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy*; D010100:Oxygen / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011355:Prodrugs / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D051793:Hypoxia-Inducible Factor 1; D011355:Prodrugs; D010100:Oxygen
keywords: Hypoxia; hypoxia-activated prodrugs; imaging; oxygen; radiation