In vivo activation of the hypoxia-targeted cytotoxin AQ4N in human tumor xenografts

• Published in: Molecular cancer therapeutics Vol. 8; no. 12; pp. 3266 - 3275
• Main Authors: Williams, Kaye J., Albertella, Mark R., Fitzpatrick, Brian, Loadman, Paul M., Shnyder, Steven D., Chinje, Edwin C., Telfer, Brian A., Dunk, Chris R., Harris, Peter A., Stratford, Ian J.
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01.12.2009
• Subjects: Animals; Anthraquinones - metabolism; Anthraquinones - pharmacology; Antineoplastic Agents - pharmacology; AQ4N radio/chemotherapy; Cell Line, Tumor; Chromatography, High Pressure Liquid; Cisplatin - pharmacology; Combined Modality Therapy; Cytotoxins - metabolism; Cytotoxins - pharmacology; Drug Synergism; experimental tumors; Female; Humans; Hypoxia; Mass Spectrometry; Mice; Mice, Nude; Microscopy, Confocal; Neoplasms - metabolism; Neoplasms - pathology; Neoplasms - therapy; preclinical; prodrug; Prodrugs - metabolism; Prodrugs - pharmacology; Radiotherapy - methods; Treatment Outcome; Xenograft Model Antitumor Assays

AQ4N (banoxantrone) is a prodrug that, under hypoxic conditions, is enzymatically converted to a cytotoxic DNA-binding agent, AQ4. Incorporation of AQ4N into conventional chemoradiation protocols therefore targets both oxygenated and hypoxic regions of tumors, and potentially will increase the effec...