Cited by 1,051DNA Repair MechanismsPARP inhibition in cancer therapyCancer-related Molecular Pathways

DNA repair dysregulation from cancer driver to therapeutic target

Open access
Curtin, Nicola J.·2012·Nature Reviews Cancer

Abstract

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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Crossref · 10.1038/nrc3399

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Authors
Curtin, N. J.
Affiliations
Newcastle University (GB)
Corresponding author
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
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

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