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The DNA damage response and cancer therapy

Abstract

Genomic instability is one of the most pervasive characteristics of tumour cells and is probably the combined effect of DNA damage, tumour-specific DNA repair defects, and a failure to stop or stall the cell cycle before the damaged DNA is passed on to daughter cells. Although these processes drive genomic instability and ultimately the disease process, they also provide therapeutic opportunities. A better understanding of the cellular response to DNA damage will not only inform our knowledge of cancer development but also help to refine the classification as well as the treatment of the disease.

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Figure 1: A panoply of DNA repair mechanisms maintains genomic stability.
Figure 2: Genomic scars in cancer.

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Acknowledgements

We thank Cancer Research UK, The Wellcome Trust, Breakthrough Breast Cancer, AACR, The Komen Foundation, The Breast Cancer Research Foundation, the European Union and The Breast Cancer Campaign for funding the work in our laboratory. We also acknowledge NHS funding to the Royal Marsden Hospital NIHR Biomedical Research Centre.

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Correspondence to Christopher J. Lord or Alan Ashworth.

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C.J.L. and A.A. are named inventors on patents describing the use of PARP inhibitors and may stand to gain under the ICR, 'Rewards to Inventors Scheme'.

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Lord, C., Ashworth, A. The DNA damage response and cancer therapy. Nature 481, 287–294 (2012). https://doi.org/10.1038/nature10760

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