DNA repair dysregulation from cancer driver to therapeutic target
Open accessAbstract
Dysregulation of DNA damage repair and signalling to cell cycle checkpoints, known as the DNA damage response (DDR), is associated with a predisposition to cancer and affects responses to DNA-damaging anticancer therapy. Dysfunction of one DNA repair pathway may be compensated for by the function of another compensatory DDR pathway, which may be increased and contribute to resistance to DNA-damaging chemotherapy and radiotherapy. Therefore, DDR pathways make an ideal target for therapeutic intervention; first, to prevent or reverse therapy resistance; and second, using a synthetic lethal approach to specifically kill cancer cells that are dependent on a compensatory DNA repair pathway for survival in the context of cancer-associated oxidative and replicative stress. These hypotheses are currently being tested in the laboratory and are being translated into clinical studies.
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Components of DNA repair and DDR pathways have become therapeutic targets and are being tested in laboratory and clinical studies.
“factors involved in DNA repair and DDR pathways have become therapeutic targets and are currently being tested in both laboratory and clinical studies [151, 222]”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [151]
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- Authors
- Curtin, N. J.
- Affiliations
- Newcastle University (GB)
- Corresponding author
- Curtin, Nicola J.
- ORCID
- Curtin, Nicola J.
- Venue
- Nature Reviews Cancer
- Published
- 2012-11-23
- Volume
- 12
- Issue
- 12
- Pages
- 801-817
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- OpenAlex
- W2083960841
- Cited by
- 1,051
- References
- 202
- Citations by year
- 2026: 24 · 2025: 54 · 2024: 67 · 2023: 79 · 2022: 81 · 2021: 127 · 2020: 90 · 2019: 88 · 2018: 72 · 2017: 90 · 2016: 77 · 2015: 80 · 2014: 66 · 2013: 55 · 2012: 1
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Pfizer
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- DNA damage response, DNA repair, synthetic lethality, cell cycle checkpoints, radiotherapy resistance, cancer susceptibility, oxidative stress, replicative stress
- MeSH terms
- Animals, Antineoplastic Agents, DNA Damage, DNA Repair, Humans, Neoplasms, Signal Transduction, Biomarkers, Cell Cycle Checkpoints, Homologous Recombination
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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