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Chem Biol. 2013 May 23;20(5):648-59. doi: 10.1016/j.chembiol.2013.04.007.

DNA-damaging agents in cancer chemotherapy: serendipity and chemical biology.

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Department of Molecular Genetics and the Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.


DNA-damaging agents have a long history of use in cancer chemotherapy. The full extent of their cellular mechanisms, which is essential to balance efficacy and toxicity, is often unclear. In addition, the use of many anticancer drugs is limited by dose-limiting toxicities as well as the development of drug resistance. Novel anticancer compounds are continually being developed in the hopes of addressing these limitations; however, it is essential to be able to evaluate these compounds for their mechanisms of action. This review covers the current DNA-damaging agents used in the clinic, discusses their limitations, and describes the use of chemical genomics to uncover new information about the DNA damage response network and to evaluate novel DNA-damaging compounds.

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