AQ4N: a new approach to hypoxia-activated cancer chemotherapy

LH Patterson, Stephanie McKeown

Research output: Contribution to journalArticlepeer-review

169 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.
Original languageEnglish
Pages (from-to)1589-1593
JournalBRITISH JOURNAL OF CANCER
Volume83
Issue number12
DOIs
Publication statusPublished (in print/issue) - Dec 2000

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