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Radiation Sensitizers: A Selective Review of Molecules Targeting DNA and non-DNA Targets

H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida

The ideal radiation sensitizer would reach the tumor in adequate concentrations and act selectively in the tumor compared with normal tissue. It would have predictable pharmacokinetics for timing with radiation treatment and could be administered with every radiation treatment. The ideal radiation sensitizer would have minimal toxicity itself and minimal or manageable enhancement of radiation toxicity. The ideal radiation sensitizer does not exist today. This review outlines the concept of combining 2 modalities of cancer treatment, radiation and drug therapy, to provide enhanced tumor cell kill in the treatment of human malignancies and discusses molecules that target DNA and non-DNA targets. Combining drugs that have unique mechanisms of action and absence of overlapping toxicities with systemically administered radiotherapy should be exploited in future clinical trials. This is an exciting time in clinical oncology research, because we have a plethora of new molecules to evaluate.

Key Words: radiation sensitizers • 5-fluorouracil • platinum • gemcitabine • topoisomerase • epidermal growth factor inhibitors • vascular endothelial growth factor inhibitors