Exploiting Tumor Hypoxia in the Treatment of Solid Tumors

Abstract

Studies have shown that reduced oxygen tension (hypoxia) in solid tumors adversely affects the outcome of radiotherapy and chemotherapy. Besides being an independent prognostic marker of poor treatment outcome, hypoxia represents a physiological difference that can be utilized for selective cancer treatment. Since severe hypoxia does not occur in normal tissue, it may be exploited for therapeutic gain. One strategy is to use drugs that are toxic only under hypoxic conditions, and the first drug of this class to enter clinical testing, tirapazamine, is showing considerable promise. The second way to exploit hypoxia is to take advantage of the selective induction of the transcription factor hypoxia-inducible factor 1 (HIF-1) under hypoxic conditions. Gene therapy strategies based on this concept are in development.