ArticleMolecular cancer research : MCR2016
Olaparib, Monotherapy or with Ionizing Radiation, Exacerbates DNA Damage in Normal Tissues: Insights from a New p21 Reporter Mouse.
Article in Molecular cancer research : MCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
17 citing papers in PubMed, 32 citations in OpenAlex.
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- Targeting RAD52 overcomes PARP inhibitor resistance in preclinicalbioRxiv : the preprint server for biology · 2025Article
- NovelOpen biology · 2024Article
- Mouse models to investigate in situ cell fate decisions induced by p53.The EMBO journal · 2024Article
- Increased vascular smooth muscle cell senescence in aneurysmal Fibulin-4 mutant mice.npj aging · 2024Article
- Exploiting Synthetic Lethality between Germline BRCA1 Haploinsufficiency and PARP Inhibition in JAK2V617F-Positive Myeloproliferative Neoplasms.International journal of molecular sciences · 2023Article
- In vivo stress reporters as early biomarkers of the cellular changes associated with progeria.Journal of cellular and molecular medicine · 2022Article
- Multiple functions of p21 in cancer radiotherapy.Journal of cancer research and clinical oncology · 2021Review
- VRK1 Depletion Facilitates the Synthetic Lethality of Temozolomide and Olaparib in Glioblastoma Cells.Frontiers in cell and developmental biology · 2021Article
- Lysine Methyltransferase Inhibitors Impair H4K20me2 and 53BP1 Foci in Response to DNA Damage in Sarcomas, a Synthetic Lethality Strategy.Frontiers in cell and developmental biology · 2021Article
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- Olaparib and ionizing radiation trigger a cooperative DNA-damage repair response that is impaired by depletion of the VRK1 chromatin kinase.Journal of experimental & clinical cancer research : CR · 2019Article
- Identification of anticancer drugs to radiosensitiseCancer biology & medicine · 2019Article
- Soft tissue sarcomas: new opportunity of treatment with PARP inhibitors?La Radiologia medica · 2019Review
- Transgenic Animal Models to Visualize Cancer-Related Cellular Processes by Bioluminescence Imaging.Frontiers in pharmacology · 2019Review
- Measuring in vivo responses to endogenous and exogenous oxidative stress using a novel haem oxygenase 1 reporter mouse.The Journal of physiology · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Many drugs targeting the DNA damage response are being developed as anticancer therapies, either as single agents or in combination with ionizing radiation (IR) or other cytotoxic agents. Numerous clinical trials in this area are either in progress or planned. However, concerns remain about the potential of such treatments to increase toxicity to normal tissues. In order to address this issue, a novel reporter mouse line was created through the simultaneous incorporation of multiple reporters, β-galactosidase, and firefly luciferase, into the DNA damage-inducible p21 (CDKN1A) locus. The data demonstrate that in situ β-galactosidase staining facilitates high fidelity mapping of p21 expression across multiple organs and tissues at single-cell resolution, whereas the luciferase reporter permits noninvasive bioluminescent imaging of p21 expression. This model was used to determine the capacity of a number of DNA-damaging agents, including IR, cisplatin, and etoposide to induce p21 expression in normal tissues. In addition, the PARP inhibitor olaparib was examined alone or in combination with IR as well as cisplatin. A single exposure to olaparib alone caused DNA damage to cells in the mucosal layer lining mouse large intestine. It also exacerbated DNA damage induced in this organ and the kidney by coadministered IR. These studies suggest that olaparib has carcinogenic potential and illustrate the power of this new model to evaluate the safety of new therapeutic regimens involving combination therapies. IMPLICATIONS: Olaparib causes DNA damage to normal tissues and might be a carcinogen. Mol Cancer Res; 14(12); 1195-203. ©2016 AACR.
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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.