ArticleBritish journal of cancer2018
Long-term treatment with the PARP inhibitor niraparib does not increase the mutation load in cell line models and tumour xenografts.
Article in British journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer.The Cochrane database of systematic reviews · 2022Pooled it
- Combination of PARP Inhibitor Olaparib, and PD-L1 Inhibitor Durvalumab, in Recurrent Ovarian Cancer: a Proof-of-Concept Phase II Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Neoantigen Targeting as a Novel Approach for Therapy-Resistant Tumors.Molecular diagnosis & therapy · 2026Review
- Tracking DNA damage localization and chromatin remodeling in live cells using time-resolved quantitative analysis of DNA counterstains.Cellular and molecular life sciences : CMLS · 2026Article
- Large-scale single-cell phylogenetic mapping of clonal evolution in the human aging esophagus.bioRxiv : the preprint server for biology · 2025Article
- The role of Poly-ADP ribose polymerase (PARP) enzymes in chemotherapy-induced cognitive impairments - parallels with other neurodegenerative disorders.Frontiers in pharmacology · 2025Review
- DNA mismatch repair protects the genome from oxygen-induced replicative mutagenesis.Nucleic acids research · 2023Article
- Combining PARP Inhibition and Immunotherapy in BRCA-Associated Cancers.Cancer treatment and research · 2023Article
- Article
- Exposure to escalating olaparib does not induce acquired resistance to PARPi and to other chemotherapeutic compounds in ovarian cancer cell lines.International journal of oncology · 2022Article
- Characterisation of the spectrum and genetic dependence of collateral mutations induced by translesion DNA synthesis.PLoS genetics · 2022Article
- Mapping molecular subtype specific alterations in breast cancer brain metastases identifies clinically relevant vulnerabilities.Nature communications · 2022Article
- Deficiency of replication-independent DNA mismatch repair drives a 5-methylcytosine deamination mutational signature in cancer.Science advances · 2021Article
- Targeting the DNA damage response in immuno-oncology: developments and opportunities.Nature reviews. Cancer · 2021Review
- Poly (ADP-ribose) Polymerase Inhibition in Patients with Breast Cancer and BRCA 1 and 2 Mutations.Drugs · 2020Review
- PARP Inhibitor Efficacy Depends on CD8Cancer discovery · 2019Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundPoly-ADP ribose polymerase (PARP) inhibitor-based cancer therapy selectively targets cells with deficient homologous recombination repair. Considering their long-term use in maintenance treatment, any potential mutagenic effect of PARP inhibitor treatment could accelerate the development of resistance or harm non-malignant somatic cells.
methodsWe tested the mutagenicity of long-term treatment with the PARP inhibitor niraparib using whole-genome sequencing of cultured cell clones and whole-exome sequencing of patient-derived breast cancer xenografts.
resultsWe observed no significant increase in the number and alteration in the spectrum of base substitutions, short insertions and deletions and genomic rearrangements upon niraparib treatment of human DLD-1 colon adenocarcinoma cells, wild-type and BRCA1 mutant chicken DT40 lymphoblastoma cells and BRCA1-defective SUM149PT breast carcinoma cells, except for a minor increase in specific deletion classes. We also did not detect any contribution of in vivo niraparib treatment to subclonal mutations arising in breast cancer-derived xenografts.
conclusionsThe results suggest that long-term inhibition of DNA repair with PARP inhibitors has no or only limited mutagenic effect. Mutagenesis due to prolonged use of PARP inhibitors in cancer treatment is therefore not expected to contribute to the genetic evolution of resistance, generate significant immunogenic neoepitopes or induce secondary malignancies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.