Therapeutic opportunities within the DNA damage response

Pearl, Laurence H, Schierz, Amanda C, Ward, Simon E, Al-Lazikani, Bissan and Pearl, Frances M G (2015) Therapeutic opportunities within the DNA damage response. Nature Reviews Cancer, 15. pp. 166-180. ISSN 1474-175X

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Abstract

The DNA damage response (DDR) is essential for maintaining the genomic integrity of the cell, and its disruption is one of the hallmarks of cancer. Classically, defects in the DDR have been exploited therapeutically in the treatment of cancer with radiation therapies or genotoxic chemotherapies. More recently, protein components of the DDR systems have been identified as promising avenues for targeted cancer therapeutics. Here, we present an in-depth analysis of the function, role in cancer and therapeutic potential of 450 expert-curated human DDR genes. We discuss the DDR drugs that have been approved by the US Food and Drug Administration (FDA) or that are under clinical investigation. We examine large-scale genomic and expression data for 15 cancers to identify deregulated components of the DDR, and we apply systematic computational analysis to identify DDR proteins that are amenable to modulation by small molecules, highlighting potential novel therapeutic targets.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QH Natural history > QH0301 Biology
Depositing User: Tom Gittoes
Date Deposited: 06 Mar 2015 10:46
Last Modified: 25 Mar 2017 13:50
URI: http://sro.sussex.ac.uk/id/eprint/53247

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