ArticleOncotarget2016
Targeting DNA double strand break repair with hyperthermia and DNA-PKcs inhibition to enhance the effect of radiation treatment.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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
28 citing papers in PubMed, 48 citations in OpenAlex.
- BUB1B promotes homologous recombination‑mediated DNA damage repair in breast cancer cells through the PI3K/AKT signaling pathway.Oncology reports · 2025Article
- Research progress on new physical therapies for cancer (Review).Oncology letters · 2025Review
- Review
- Translation regulatory long non-coding RNA 1 negatively regulates cell radiosensitivity via the miR-22-3p/SP1 axis in non-small cell lung cancer.The clinical respiratory journal · 2024Article
- Nanoparticle-Mediated Hyperthermia and Cytotoxicity Mechanisms in Cancer.International journal of molecular sciences · 2023Review
- Valproic acid radiosensitizes anaplastic thyroid cells through a decrease of the DNA damage repair capacity.Journal of endocrinological investigation · 2023Article
- Combination Therapy of Radiation and Hyperthermia, Focusing on the Synergistic Anti-Cancer Effects and Research Trends.Antioxidants (Basel, Switzerland) · 2023Review
- Primary Founder Mutations in theInternational journal of molecular sciences · 2022Article
- Recent progress of the tumor microenvironmental metabolism in cervical cancer radioresistance.Frontiers in oncology · 2022Review
- DNA damage and metabolic mechanisms of cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- DNA double-strand breaks repair inhibitors potentiates the combined effect of VP-16 and CDDP in human colorectal adenocarcinoma (LoVo) cells.Molecular biology reports · 2021Article
- Establishment of Tumor Treating Fields Combined With Mild Hyperthermia as Novel Supporting Therapy for Pancreatic Cancer.Frontiers in oncology · 2021Article
- DNA damage repair functions and targeted treatment in breast cancer.Breast cancer (Tokyo, Japan) · 2020Review
- DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer.Signal transduction and targeted therapy · 2020Review
- Integrating Loco-Regional Hyperthermia Into the Current Oncology Practice: SWOT and TOWS Analyses.Frontiers in oncology · 2020Review
- Cellular Stress Responses in Radiotherapy.Cells · 2019Review
- Differential Expression of DNA Repair Genes in Prognostically-Favorable versus Unfavorable Uveal Melanoma.Cancers · 2019Article
- Ultrasound Hyperthermia Technology for Radiosensitization.Ultrasound in medicine & biology · 2019Review
- Cell line-specific efficacy of thermoradiotherapy in human and canine cancer cells in vitro.PloS one · 2019Article
- New physical approaches to treat cancer stem cells: a review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Radiotherapy is based on the induction of lethal DNA damage, primarily DNA double-strand breaks (DSB). Efficient DSB repair via Non-Homologous End Joining or Homologous Recombination can therefore undermine the efficacy of radiotherapy. By suppressing DNA-DSB repair with hyperthermia (HT) and DNA-PKcs inhibitor NU7441 (DNA-PKcsi), we aim to enhance the effect of radiation.The sensitizing effect of HT for 1 hour at 42°C and DNA-PKcsi [1 μM] to radiation treatment was investigated in cervical and breast cancer cells, primary breast cancer sphere cells (BCSCs) enriched for cancer stem cells, and in an in vivo human tumor model. A significant radio-enhancement effect was observed for all cell types when DNA-PKcsi and HT were applied separately, and when both were combined, HT and DNA-PKcsi enhanced radio-sensitivity to an even greater extent. Strikingly, combined treatment resulted in significantly lower survival rates, 2 to 2.5 fold increase in apoptosis, more residual DNA-DSB 6 h post treatment and a G2-phase arrest. In addition, tumor growth analysis in vivo showed significant reduction in tumor growth and elevated caspase-3 activity when radiation was combined with HT and DNA-PKcsi compared to radiation alone. Importantly, no toxic side effects of HT or DNA-PKcsi were found.In conclusion, inhibiting DNA-DSB repair using HT and DNA-PKcsi before radiotherapy leads to enhanced cytotoxicity in cancer cells. This effect was even noticed in the more radio-resistant BCSCs, which are clearly sensitized by combined treatment. Therefore, the addition of HT and DNA-PKcsi to conventional radiotherapy is promising and might contribute to more efficient tumor control and patient outcome.
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Registered trials
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