Journal
BRITISH JOURNAL OF CANCER
Volume 83, Issue 12, Pages 1589-1593Publisher
NATURE PUBLISHING GROUP
DOI: 10.1054/bjoc.2000.1564
Keywords
bioreductive; prodrug; topoisomerase II; in vivo; AQ4N; tirapazamine
Categories
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available