AQ4N: a new approach to hypoxia-activated cancer chemotherapy

LH Patterson, Stephanie McKeown

    Research output: Contribution to journalArticle

    107 Citations (Scopus)

    Abstract

    Preclinical studies demonstrate that in vivo AQ4N enhances the anti-tumour effects of radiation and chemotherapeutic agents with a dose-modifying factor of approximately 2.0. With careful scheduling no, or very little, additional normal tissue toxicity should be observed. AQ4N is a bioreductive prodrug of a potent, stable, reduction product which binds non-covalently to DNA, facilitating antitumour activity in both hypoxic and proximate oxic tumour cells. AQ4N is clearly different in both its mechanism of action and potential bystander effect compared to previously identified bioreductive drugs. In particular AQ4N is the only bioreductive prodrug topoisomerase II inhibitor to enter clinical trials. Targeting this enzyme, which is crucial to cell division, may help sensitize tumours to repeated (fractionated) courses of radiotherapy. This is because in principle, the bioreduction product of AQ4N can inhibit the topoisomerase activity of hypoxic cells as they attempt to re-enter the cell cycle. (C) 2000 Cancer Research Campaign.
    LanguageEnglish
    Pages1589-1593
    JournalBRITISH JOURNAL OF CANCER
    Volume83
    Issue number12
    DOIs
    Publication statusPublished - Dec 2000

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    Drug Therapy
    Prodrugs
    Neoplasms
    Bystander Effect
    Topoisomerase II Inhibitors
    Radiation Effects
    Cell Division
    Action Potentials
    Cell Cycle
    Radiotherapy
    AQ4N
    Hypoxia
    Clinical Trials
    DNA
    Enzymes
    Pharmaceutical Preparations

    Cite this

    Patterson, LH ; McKeown, Stephanie. / AQ4N: a new approach to hypoxia-activated cancer chemotherapy. In: BRITISH JOURNAL OF CANCER. 2000 ; Vol. 83, No. 12. pp. 1589-1593.
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    AQ4N: a new approach to hypoxia-activated cancer chemotherapy. / Patterson, LH; McKeown, Stephanie.

    In: BRITISH JOURNAL OF CANCER, Vol. 83, No. 12, 12.2000, p. 1589-1593.

    Research output: Contribution to journalArticle

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