AQ4N: a new approach to hypoxia-activated cancer chemotherapy

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 prod...

Full description

Saved in:
Bibliographic Details
Published inBritish journal of cancer Vol. 83; no. 12; pp. 1589 - 1593
Main Authors PATTERSON, L. H, MCKEOWN, S. R
Format Journal Article
LanguageEnglish
Published Basingstoke Nature Publishing Group 01.12.2000
Subjects
Animals
Anthraquinones - therapeutic use
Antineoplastic agents
Antineoplastic Agents - therapeutic use
Biological and medical sciences
Cancer research
Cancer therapies
Cell cycle
Cell division
Cell Hypoxia
Chemotherapy
Cytotoxicity
Humans
Hypoxia
Medical research
Medical sciences
Mini-Review
Neoplasms - drug therapy
Neoplasms, Experimental - drug therapy
Pharmacology. Drug treatments
Phosphates
Physical properties
Prodrugs - therapeutic use
Radiation-Protective Agents - therapeutic use
Toxicity
Tumors
Antineoplastic agent
DNA topoisomerase (ATP-hydrolysing)
Oxygen
Anthraquinone derivatives
Enzyme
Rodentia
Enzyme inhibitor
Prodrug
Malignant tumor
Vertebrata
Chemotherapy
Isomerases
Mammalia
Treatment
Bioreductive drug
Mouse
Animal
Hypoxia
Online AccessGet full text

Cover

More Information
Summary: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.
ISSN:0007-0920
1532-1827
DOI:10.1054/bjoc.2000.1564