Normal tissue protection in cancer therapy - Progress and prospects

Normal tissue tolerance is a major dose-limiting factor in radiotherapy and chemotherapy of cancer. During the past few decades several investigations have been directed toward increasing normal tissue tolerance by using chemical protectors against radiation and drug toxicity. WR-2721, the phosphorylated aminothiol, synthesized in the 1960s, has been hailed as the best chemical protector discovered so far. But its systemic toxicity after repeated administration in cancer patients during clinical trials has been a deterrent against its acceptance in routine radiotherapy, though more encouraging results have been reported with chemotherapy. The 1980s found a surge of activity in the field of chemical protection research, which has resulted in the discovery of many non-thiol protectors, particularly the biological response modifiers and antioxidants. It has also been found that protection by WR-2721 can be improved and its toxicity reduced by combination with some low potent protective chemicals. This review analyzes the major reports on chemical protectors published during the past ten years.