Cited by 587DNA Repair MechanismsCancer-related Molecular PathwaysCancer Genomics and Diagnostics

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Therapeutic opportunities within the DNA damage response

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Pearl, Laurence H., Schierz, Amanda C., Ward, Simon E., Al-Lazikani, Bissan, Pearl, Frances M. G.·2015·Nature Reviews Cancer

DOI 10.1038/nrc3891

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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.

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Authors: Pearl, L. H., Schierz, A. C., Ward, S. E., Al-Lazikani, B., & Pearl, F. M. G.
Affiliations: University of Sussex (GB)
Institute of Cancer Research (GB)
Corresponding author: Pearl, Frances M. G.
ORCID: Pearl, Laurence H.
Ward, Simon E.
Pearl, Frances M. G.
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2015-02-24
Volume: 15
Issue: 3
Pages: 166-180
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc3891
OpenAlex: W2065087624
Cited by: 587
References: 112
Citations by year: 2026: 22 · 2025: 42 · 2024: 66 · 2023: 56 · 2022: 57 · 2021: 66 · 2020: 59 · 2019: 49 · 2018: 49 · 2017: 60 · 2016: 45 · 2015: 16
FWCI: 5.49
Type: journal article
Language: en
Open access: green
figshare.com
Licence: cc-by
www.springer.com/tdm (tdm)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Sussex Research Online (University of Sussex) (submittedVersion)
Figshare (submittedVersion, cc-by)
ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Funders: Cancer Research UK (C309/A11566, 11566, C302/A14532, 14532)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords: DNA damage response, synthetic lethality, targeted cancer therapy, therapeutic target, genome stability, cancer genomics
MeSH terms: DNA Damage, DNA Repair, Humans, Neoplasms

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