Cited by 622DNA Repair MechanismsPARP inhibition in cancer therapyChromatin Remodeling and Cancer

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The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance

Bouwman, Peter, Jonkers, Jos·2012·Nature Reviews Cancer

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Abstract

Tumours with specific DNA repair defects can be completely dependent on back-up DNA repair pathways for their survival. This dependence can be exploited therapeutically to induce synthetic lethality in tumour cells. For instance, homologous recombination (HR)-deficient tumours can be effectively targeted by DNA double-strand break-inducing agents. However, not all HR-defective tumours respond equally well to this type of therapy. Tumour cells may acquire resistance by invoking biochemical mechanisms that reduce drug action or by acquiring additional alterations in DNA damage response pathways. A thorough understanding of these processes is important for predicting treatment response and for the development of novel treatment strategies that prevent the emergence of therapy-resistant tumours.

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Authors: Bouwman, P., & Jonkers, J.
Affiliations: The Netherlands Cancer Institute (NL)
Corresponding author: Jonkers, Jos
ORCID: Bouwman, Peter
Jonkers, Jos
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2012-08-24
Volume: 12
Issue: 9
Pages: 587-598
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc3342
OpenAlex: W1980438635
Cited by: 615
References: 151
Citations by year: 2026: 20 · 2025: 31 · 2024: 43 · 2023: 40 · 2022: 52 · 2021: 47 · 2020: 56 · 2019: 29 · 2018: 46 · 2017: 56 · 2016: 52 · 2015: 43 · 2014: 53 · 2013: 44 · 2012: 3
FWCI: 4.17
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Funders: European Commission
KWF Kankerbestrijding
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: DNA damage response, chemoresistance, synthetic lethality, homologous recombination deficiency, DNA repair deficiency, acquired drug resistance
MeSH terms: Antineoplastic Agents, DNA Damage, DNA Repair, Neoplasms, Signal Transduction, Genes, p53, Drug Resistance, Neoplasm

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The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance

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