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

  • Dean T. Williams
  • Christopher J. StaplesEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1007)


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.


PARP DNA repair Synthetic lethality Cancer Mitochondria Ageing 


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Copyright information

© American Association of Pharmaceutical Scientists 2017

Authors and Affiliations

  1. 1.School of Medical SciencesBangor UniversityBangorUK
  2. 2.Department of Vascular SurgeryYsbyty GwyneddBangorUK

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