The role of hypoxia-activated prodrugs in cancer therapy.
Tumour hypoxia, a deficiency of oxygen due to an inefficient vasculature, is a limiting factor in both the radiotherapy and chemotherapy of solid tumours. Paradoxically, it is also an attractive therapeutic target, because severe hypoxia occurs only in solid tumour tissue. Hypoxic cells can be exploited for therapy by non-toxic, hypoxia-activated prodrugs. Conceptually, 'trigger' units in these drugs are selectively activated in hypoxic cells to release or activate a toxic 'effector', capable of killing surrounding oxygenated tumour cells. Useful triggers include nitroaromatics, quinones, N-oxides, and transition metals. The N-oxide tirapazamine is in phase III clinical trials.
Denny
W A
WA
Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand. b.denny@auckland.ac.nz
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D015687:Cell Hypoxia; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009593:Nitroimidazoles; D010087:Oxides; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology; D011809:Quinones
D000970:Antineoplastic Agents; D009593:Nitroimidazoles; D010087:Oxides; D011355:Prodrugs; D011809:Quinones