ArticleInternational journal of radiation oncology, biology, physics2019
Nonhomologous End Joining Is More Important Than Proton Linear Energy Transfer in Dictating Cell Death.
Article in International journal of radiation oncology, biology, physics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Does particle radiation have superior radiobiological advantages for prostate cancer cells? A systematic review of in vitro studies.European journal of medical research · 2022Pooled it
- Article
- Distinct molecular responses of human intestinal organoids to proton and photon radiation.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Differentiation Stage Predicts Radiosensitivity in Mesenchymal-Like Pancreatic Cancer.International journal of radiation oncology, biology, physics · 2025Article
- Assessing the Relative Contribution of DSB Repair Proteins as a Function of LET.International journal of particle therapy · 2025Article
- Position in proton Bragg curve influences DNA damage complexity and survival in head and neck cancer cells.Clinical and translational radiation oncology · 2025Article
- Enhanced radiosensitivity of head and neck cancer cells to proton therapy via hyperthermia-induced homologous recombination deficiency.Clinical and translational radiation oncology · 2025Article
- NRG Oncology White Paper on the Relative Biological Effectiveness in Proton Therapy.International journal of radiation oncology, biology, physics · 2025Review
- PARP inhibition radiosensitizes BRCA1 wildtype and mutated breast cancer to proton therapy.Scientific reports · 2024Article
- Multi-Target Inhibitor CUDC-101 Impairs DNA Damage Repair and Enhances Radiation Response in Triple-Negative Breast Cell Line.Pharmaceuticals (Basel, Switzerland) · 2024Article
- ATR inhibition radiosensitizes cells through augmented DNA damage and G2 cell cycle arrest abrogation.JCI insight · 2024Article
- Potential Benefits of Combining Proton or Carbon Ion Therapy with DNA Damage Repair Inhibitors.Cells · 2024Review
- Olaparib enhances sensitization of BRCA-proficient breast cancer cells to x-rays and protons.Breast cancer research and treatment · 2024Article
- Alpha Particle-Emitting Radiopharmaceuticals as Cancer Therapy: Biological Basis, Current Status, and Future Outlook for Therapeutics Discovery.Molecular imaging and biology · 2023Review
- Targeted Inhibition of DNA-PKcs, ATM, ATR, PARP, and Rad51 Modulate Response to X Rays and Protons.Radiation research · 2022Article
- An empirical model of proton RBE based on the linear correlation between x-ray and proton radiosensitivity.Medical physics · 2022Article
- An Integrated Approach Reveals DNA Damage and Proteotoxic Stress as Main Effects of Proton Radiation inInternational journal of molecular sciences · 2022Article
- Ganetespib selectively sensitizes cancer cells for proximal and distal spread-out Bragg peak proton irradiation.Radiation oncology (London, England) · 2022Article
- Particle Therapy for Breast Cancer.Cancers · 2022Review
- Outcomes After Breast Radiation Therapy in a Diverse Patient Cohort With a Germline BRCA1/2 Mutation.International journal of radiation oncology, biology, physics · 2022Article
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Authors and funding
13 authors.
Funding
Abstract
purposeThis study seeks to identify biological factors that may yield a therapeutic advantage of proton therapy versus photon therapy. Specifically, we address the role of nonhomologous end-joining (NHEJ) and homologous recombination (HR) in the survival of cells in response to clinical photon and proton beams. METHODS AND MATERIALS: We irradiated HT1080, M059K (DNA-PKcs
resultsOur results indicate that NHEJ deficiency is more important in dictating cell survival than proton LET. Cells with disrupted HR through BRCA1 mutation showed increased radiosensitivity only for high-LET protons whereas RAD51 depletion showed increased radiosensitivity for both photons and protons. DNA double strand breaks, assessed by γ-H2AX radiation-induced foci, showed greater numbers after 24 hours in cells exposed to higher LET protons. We also observed that NHEJ-deficient cells were unable to repair the vast majority of double strand breaks after 24 hours.
conclusionsBRCA1 mutation significantly sensitizes cells to protons, but not photons. Loss of NHEJ renders cells hypersensitive to radiation, whereas the relative importance of HR increases with LET across several cell lines. This may be attributable to the more clustered damage induced by higher LET protons, which are harder to repair through NHEJ. This highlights the importance of tumor biology in dictating treatment modality and suggests BRCA1 as a potential biomarker for proton therapy response. Our data also support the use of pharmacologic inhibitors of DNA repair to enhance the sensitivity to different radiation types, although this raises issues for normal tissue toxicity.
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