Bioreductive and gene therapy approaches to hypoxic diseases

    Research output: Chapter in Book/Report/Conference proceedingChapter

    Abstract

    Hypoxia is a feature that exists in most, if not all, solid tumours and hypoxia has been shown to exist in a variety of other diseases. Bioreductive prodrugs have been developed to preferentially target the hypoxic cells in tumours. They are prodrugs, that are reductively activated (catalysed by reductive enzymes) to afford their active (toxic) species. More recently, bioreductive delivery agents that 'release' a therapeutic entity preferentially under hypoxic conditions have also been developed to target hypoxia, not only in tumours, but also in a host of other diseases. This new technology platform is described in this review. In addition, we discuss the potential of utilising hypoxia to deliver selective gene therapy based upon the transcription factor HIF-1 and the use of unique genetic sequences termed HRE's (hypoxia responsive elements) that specifically control gene expression under hypoxic conditions. Finally, we describe how these drugs and gene-based therapeutic approaches can be combined to potentially deliver a highly selective form of therapy for cancer and other diseases where hypoxia plays a major pathophysiological role. © 2001 Elsevier Science B.V. All rights reserved.
    Original languageEnglish
    Title of host publicationAdvanced Drug Delivery Reviews|Adv. Drug Deliv. Rev.
    Pages217-228
    Number of pages11
    Volume53
    DOIs
    Publication statusPublished - 17 Dec 2001

    Keywords

    • Antibody-directed enzyme prodrug therapy (ADEPT)
    • Benzoquinone
    • Bioreductive
    • Delivery agents
    • Gene therapy
    • Gene-directed enzyme prodrug therapy (GDEPT)
    • HIF-1α
    • Hypoxia
    • Hypoxia inducible factor (HIF)
    • Hypoxia-selectivity
    • Indolequinone
    • Ischaemia
    • Naphthoquinone
    • Nitroaromatic
    • Nitroheterocyclic
    • Nitroimidazole
    • Prodrugs
    • Quinone
    • Reductive activation
    • Reductive enzymes

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