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Targeting abnormal DNA double strand break repair in cancer

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Abstract

A major challenge in cancer treatment is the development of therapies that target cancer cells with little or no toxicity to normal tissues and cells. Alterations in DNA double strand break (DSB) repair in cancer cells include both elevated and reduced levels of key repair proteins and changes in the relative contributions of the various DSB repair pathways. These differences can result in increased sensitivity to DSB-inducing agents and increased genomic instability. The development of agents that selectively inhibit the DSB repair pathways that cancer cells are more dependent upon will facilitate the design of therapeutic strategies that exploit the differences in DSB repair between normal and cancer cells. Here, we discuss the pathways of DSB repair, alterations in DSB repair in cancer, inhibitors of DSB repair and future directions for cancer therapies that target DSB repair.

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Acknowledgments

Work in the Tomkinson laboratory is supported by grants from the National Institutes for Health (R01 GM47251, R01 GM57479, R01 ES12512 and P01 CA92584). Work in the Rassool Laboratory is supported by grants from the Leukemia Lymphoma Society (LLS 6085-07), NIH/NCI 5R01CA125635-02, State of Maryland 08072925 and V Foundation.

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Correspondence to Alan E. Tomkinson.

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Rassool, F.V., Tomkinson, A.E. Targeting abnormal DNA double strand break repair in cancer. Cell. Mol. Life Sci. 67, 3699–3710 (2010). https://doi.org/10.1007/s00018-010-0493-5

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