title: Targeting hypoxia in the treatment of small cell lung cancer.
abstract: Small cell lung cancer (SCLC) is an extremely aggressive disease for which minimal therapeutic improvements have been made over the last few decades. Patients still rely on non-targeted, chemotherapeutic drugs complemented by irradiation. Although initial response is very good, the majority of SCLC patients invariably relapse with therapy-resistant tumours. Despite the link between pathologically low oxygen levels and therapy resistant tumours, hypoxia has gained little attention in the development of novel therapies for SCLC. In contrast, the advantages of targeting hypoxic cells in many other cancer types have been studied extensively. This review describes the reasons for targeting hypoxia in SCLC and outlines strategies undertaken to enhance hypoxic tumour cell death, including the use of bioreductive prodrugs, the targeting of HIF-1α and the induction of cell death through acidosis. Therapy directed towards hypoxic tumour regions has the potential to greatly enhance the response of SCLC tumours to current treatment regimens and represents an area of research in need of greater attention. Such research could lead to the much sought after development of targeted drugs against SCLC tumours.
authors.affiliation: Faculty of Life Sciences, Manchester Academic Health Sciences Centre, University of Manchester, AV Hill Building, Manchester M13 9PT, UK; Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, AV Hill Building, Manchester M13 9PT, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: Bryant
authors.affiliation: Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, AV Hill Building, Manchester M13 9PT, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Meredith
authors.affiliation: Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, AV Hill Building, Manchester M13 9PT, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Williams
authors.affiliation: Faculty of Life Sciences, Manchester Academic Health Sciences Centre, University of Manchester, AV Hill Building, Manchester M13 9PT, UK; Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, AV Hill Building, Manchester M13 9PT, UK. Electronic address: awhite@manchester.ac.uk.
authors.forename: A
authors.initials: A
authors.lastname: White
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents
keywords: Acidosis; Bioreductive prodrugs; HIF-1α; Hypoxia; Resistance; Small cell lung cancer; Targeted therapy