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Therapeutic opportunities within the DNA damage response

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posted on 2023-06-08, 20:14 authored by Laurence PearlLaurence Pearl, Amanda C Schierz, Simon E Ward, Bissan Al-Lazikani, Frances PearlFrances Pearl
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.

History

Publication status

  • Published

File Version

  • Submitted version

Journal

Nature Reviews Cancer

ISSN

1474-175X

Publisher

Nature Publishing Group

Issue

3

Volume

15

Page range

166-180

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-03-06

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