ArticleThe Journal of clinical investigation2020
Selective DNA-PKcs inhibition extends the therapeutic index of localized radiotherapy and chemotherapy.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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.
The trial behind it
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
50 citing papers in PubMed, 65 citations in OpenAlex.
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Selective mRNA translation determines adaptative mutability of melanoma cells to anti-BRAF/MEK combination therapy.EMBO molecular medicine · 2026Article
- Targeting DNA-PK: medicinal chemistry insights into small-molecule inhibitor discovery and optimisation.RSC medicinal chemistry · 2026Review
- DNA-PKcs promotes therapy resistance and metastatic recurrence in neuroblastoma.Cancer letters · 2026Article
- Synergistic Effects of DNA-PKcs Inhibition and Radiotherapy in Esophageal Squamous Cell Carcinoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Multi-scale in-silico modelling to unveil structural requirements for DNA-PK inhibitors as radiosensitizers and MolSHAP based design of novel ligands.Journal of computer-aided molecular design · 2025Article
- FOSL1-PRMT1 transcriptional-epigenetic circuit promotes glioblastoma radioresistance via calcyphosine-mediated DNA repair and invasion.Molecular biomedicine · 2025Article
- CNOT7 facilitates radiation resistance in colorectal cancer through TRIM21/XRCC6-mediated non-homologous end joining repair.Cell death & disease · 2025Article
- Research Advances of the Autophagy-Regulated Radiosensitivity.Cell proliferation · 2025Review
- NClinical and translational medicine · 2025Article
- An organotypic model for investigating drug-radiation responses in the lung.Journal of biological methods · 2025Article
- Disruption of RNA Splicing Increases Vulnerability of Cells to DNA-PK Inhibitors.International journal of molecular sciences · 2024Article
- Article
- Identification of 6-Anilino Imidazo[4,5-Journal of medicinal chemistry · 2024Article
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- DNA-PK participates in pre-rRNA biogenesis independent of DNA double-strand break repair.Nucleic acids research · 2024Article
- Orthotopic and metastatic tumour models in preclinical cancer research.Pharmacology & therapeutics · 2024Review
- Phase I study of peposertib and avelumab with or without palliative radiotherapy in patients with advanced solid tumors.ESMO open · 2024Article
- Selective inhibition of DNA ligase IV provides additional efficacy to the treatment of anaplastic thyroid cancer.Frontiers in oncology · 2024Article
- Hyper-Dependence on NHEJ Enables Synergy between DNA-PK Inhibitors and Low-Dose Doxorubicin in Leiomyosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
Corrections and comments
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Authors and funding
23 authors at 4 institutions in 1 country.
Funding
Abstract
Potentiating radiotherapy and chemotherapy by inhibiting DNA damage repair is proposed as a therapeutic strategy to improve outcomes for patients with solid tumors. However, this approach risks enhancing normal tissue toxicity as much as tumor toxicity, thereby limiting its translational impact. Using NU5455, a newly identified highly selective oral inhibitor of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity, we found that it was indeed possible to preferentially augment the effect of targeted radiotherapy on human orthotopic lung tumors without influencing acute DNA damage or a late radiation-induced toxicity (fibrosis) to normal mouse lung. Furthermore, while NU5455 administration increased both the efficacy and the toxicity of a parenterally administered topoisomerase inhibitor, it enhanced the activity of doxorubicin released locally in liver tumor xenografts without inducing any adverse effect. This strategy is particularly relevant to hepatocellular cancer, which is treated clinically with localized drug-eluting beads and for which DNA-PKcs activity is reported to confer resistance to treatment. We conclude that transient pharmacological inhibition of DNA-PKcs activity is effective and tolerable when combined with localized DNA-damaging therapies and thus has promising clinical potential.
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Registered trials
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.