ArticleRadiation research2022
Targeted Inhibition of DNA-PKcs, ATM, ATR, PARP, and Rad51 Modulate Response to X Rays and Protons.
Article in Radiation research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- 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
- Modeling meningioma in vitro in the omics era.Human cell · 2026Review
- Molecular insights into DNA damage response plasticity in glioma stem cells.Communications biology · 2026Review
- PARP Inhibitors as Radiosensitizers: Current Evidence and Future Directions.Current oncology reports · 2026Review
- Review
- Review
- Inhibition of ATM, ATR and DNA-PK radiosensitises 3D uveal melanoma models to X-rays and proton beam therapy.Frontiers in oncology · 2026Article
- Assessing the Relative Contribution of DSB Repair Proteins as a Function of LET.International journal of particle therapy · 2025Article
- Differentiation Stage Predicts Radiosensitivity in Mesenchymal-Like Pancreatic Cancer.International journal of radiation oncology, biology, physics · 2025Article
- Unlocking the Therapeutic Potential of DNA-PKcs in Cancer: Comprehensive Insights into Mechanisms and Clinical Applications.Cancers · 2025Review
- Radiation Therapy Personalization in Cancer Treatment: Strategies and Perspectives.International journal of molecular sciences · 2025Review
- DNA-PK Inhibition Shows Differential Radiosensitization in Orthotopic GBM PDX Models Based on DDR Pathway Deficits.Molecular cancer therapeutics · 2025Article
- PARP inhibition radiosensitizes BRCA1 wildtype and mutated breast cancer to proton therapy.Scientific reports · 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
- A perspective on tumor radiation resistance following high-LET radiation treatment.Journal of cancer research and clinical oncology · 2024Review
- Olaparib enhances sensitization of BRCA-proficient breast cancer cells to x-rays and protons.Breast cancer research and treatment · 2024Article
- DNA damage and repair dependencies of ionising radiation modalities.Bioscience reports · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Small molecule inhibitors are currently in preclinical and clinical development for the treatment of selected cancers, particularly those with existing genetic alterations in DNA repair and DNA damage response (DDR) pathways. Keen interest has also been expressed in combining such agents with other targeted antitumor strategies such as radiotherapy. Radiotherapy exerts its cytotoxic effects primarily through DNA damage-induced cell death; therefore, inhibiting DNA repair and the DDR should lead to additive and/or synergistic radiosensitizing effects. In this study we screened the response to X-ray or proton radiation in cell lines treated with DDR inhibitors (DDRis) targeting ATM, ATR, DNA-PKcs, Rad51, and PARP, with survival metrics established using clonogenic assays. We observed that DDRis generate significant radiosensitization in cancer and primary cells derived from normal tissue. Existing genetic defects in cancer cells appear to be an important consideration when determining the optimal inhibitor to use for synergistic combination with radiation. We also show that while greater radiosensitization can be achieved with protons (9.9 keV/µm) combined with DDRis, the relative biological effectiveness is unchanged or in some cases reduced. Our results indicate that while targeting the DDR can significantly radiosensitize cancer cells to such combinations, normal cells may also be equally or more severely affected, depending on the DDRi used. These data highlight the importance of identifying genetic defects as predictive biomarkers of response for combination treatment.
Indexed as
Identifiers
What OpenQuestion holds
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.