The DOI matches its Crossref record; 113 of the 113 references it cites were found in a registry or an index.
Therapeutic opportunities within the DNA damage response
Open accessAbstract
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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“We found no evidence of biallelic inactivation of 52 additional genes involved in the HR pathway [12] that could account for the HR defective signatures”
From Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers (2019) · cites this paper as [12]
In the citing paper
“No evidence of biallelic inactivation in 52 HR-related genes [12] were identified in this case”
From Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers (2019) · cites this paper as [12]
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Metadata
- 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.
- Venue
- Nature Reviews Cancer
- Published
- 2015-02-24
- Volume
- 15
- Issue
- 3
- Pages
- 166-180
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- 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
- 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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