Hypoxia-Selective Targeting by the Bioreductive Prodrug AQ4N in Patients with Solid Tumors: Results of a Phase I Study

• Published in: Clinical cancer research Vol. 14; no. 4; pp. 1096 - 1104
• Main Authors: Albertella, Mark R., Loadman, Paul M., Jones, Philip H., Phillips, Roger M., Rampling, Roy, Burnet, Neil, Alcock, Chris, Anthoney, Alan, Vjaters, Egils, Dunk, Chris R., Harris, Peter A., Wong, Alvin, Lalani, Alshad S., Twelves, Chris J.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.02.2008
• Subjects: Anthraquinones - metabolism; Anthraquinones - pharmacokinetics; Anthraquinones - therapeutic use; Antineoplastic agents; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; AQ4N; Biological and medical sciences; Bioreductive prodrug; Cell Hypoxia; Excitatory Amino Acid Transporter 2 - biosynthesis; Excitatory Amino Acid Transporter 2 - drug effects; Humans; Hypoxia; Immunohistochemistry; Medical sciences; Microscopy, Confocal; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasms - drug therapy; Pharmacodynamics; Pharmacology. Drug treatments; Prodrugs - metabolism; Prodrugs - pharmacokinetics; Prodrugs - therapeutic use; Tissue Distribution; Topoisomerase II inhibitor; Tumor-targeting; Tumors; Human; Solid tumor; Target; Oxygen; Treatment; Targeting; Phase I trial; Hypoxia; Malignant tumor; Prodrug; Cancer

Purpose: AQ4N is a novel bioreductive prodrug under clinical investigation. Preclinical evidence shows that AQ4N penetrates deeply within tumors and undergoes selective activation to form AQ4, a potent topoisomerase II inhibitor, in hypoxic regions of solid tumors. This proof-of-principle, phase I s...