The role of hypoxia-activated prodrugs in cancer therapy

The Lancet Oncology
W A Denny

Abstract

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.

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