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Personalised Medicine pp 1–16Cite as

Approaches for Identifying Novel Targets in Precision Medicine: Lessons from DNA Repair

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1007))

Abstract

Genome stability is maintained by a number of elegant mechanisms, which sense and repair damaged DNA. Germline defects that compromise genomic integrity result in cancer predisposition, exemplified by rare syndromes caused by mutations in certain DNA repair genes. These individuals often exhibit other symptoms including progeria and neurodegeneration. Paradoxically, some of these deleterious genetic alterations provide novel therapeutic opportunities to target cancer cells; an excellent example of such an approach being the recent development of poly (ADP-ribose) polymerase inhibitors as the first ‘synthetic lethal’ medicine for patients with BRCA-mutant cancers. The therapeutic exploitation of synthetic lethal interactions has enabled a novel approach to personalised medicine based on continued molecular profiling of patient and tumour material. This profiling may also aid clinicians in the identification of specific drug resistance mechanisms following relapse, and enable appropriate modification of the therapeutic regimen. This chapter focuses on therapeutic strategies designed to target aspects of the DNA damage response, and examines emerging themes demonstrating mechanistic overlap between DNA repair and neurodegeneration.

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Authors and Affiliations

  1. School of Medical Sciences, Bangor University, Bangor, Gwynedd, LL57 2DG, UK

    Dean T. Williams & Christopher J. Staples

  2. Department of Vascular Surgery, Ysbyty Gwynedd, Bangor, LL57 2PW, UK

    Dean T. Williams

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  1. Krebs Institute and Sheffield Institute for Nucleic Acids, Department of Molecular Biology and Biotechnology, Firth Court, University of Sheffield, Sheffield, United Kingdom

    Sherif El-Khamisy

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Williams, D.T., Staples, C.J. (2017). Approaches for Identifying Novel Targets in Precision Medicine: Lessons from DNA Repair. In: El-Khamisy, S. (eds) Personalised Medicine. Advances in Experimental Medicine and Biology, vol 1007. Springer, Cham. https://doi.org/10.1007/978-3-319-60733-7_1

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