ArticleScientific reports2021
TP53 modulates radiotherapy fraction size sensitivity in normal and malignant cells.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 24 citations in OpenAlex.
- Efficacy and Safety of Temozolomide Combined with Radiotherapy in the Treatment of Malignant Glioma.Journal of healthcare engineering · 2022Trial
- Toward genomic personalization of breast cancer radiotherapy: foundations, challenges, and a roadmap for clinical integration.Breast (Edinburgh, Scotland) · 2026Review
- Adjuvant Radiotherapy and Breast Cancer in Patients with Li-Fraumeni Syndrome: A Critical Review.Cancers · 2025Review
- Review
- HPV and p53 Status as Precision Determinants of Head and Neck Cancer Response to DNA-PKcs Inhibition in Combination with Irradiation.Molecular cancer therapeutics · 2025Article
- Breast cancer radiobiology: The renaissance of whole breast radiation fractionation (Review).Molecular and clinical oncology · 2024Review
- APR-246 as a radiosensitization strategy for mutant p53 cancers treated with alpha-particles-based radiotherapy.Cell death & disease · 2024Article
- Impact ofJournal of radiosurgery and SBRT · 2024Article
- Epigenetic regulation of TP53 is involved in prostate cancer radioresistance and DNA damage response signaling.Signal transduction and targeted therapy · 2023Article
- Identification of an individualized therapy prognostic signature for head and neck squamous cell carcinoma.BMC genomics · 2023Article
- p53 Modulates Radiosensitivity in Head and Neck Cancers-From Classic to Future Horizons.Diagnostics (Basel, Switzerland) · 2022Review
- Radiotherapy of High-Grade Gliomas: First Half of 2021 Update with Special Reference to Radiosensitization Studies.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Recent clinical trials in breast and prostate cancer have established that fewer, larger daily doses (fractions) of radiotherapy are safe and effective, but these do not represent personalised dosing on a patient-by-patient basis. Understanding cell and molecular mechanisms determining fraction size sensitivity is essential to fully exploit this therapeutic variable for patient benefit. The hypothesis under test in this study is that fraction size sensitivity is dependent on the presence of wild-type (WT) p53 and intact non-homologous end-joining (NHEJ). Using single or split-doses of radiation in a range of normal and malignant cells, split-dose recovery was determined using colony-survival assays. Both normal and tumour cells with WT p53 demonstrated significant split-dose recovery, whereas Li-Fraumeni fibroblasts and tumour cells with defective G1/S checkpoint had a large S/G2 component and lost the sparing effect of smaller fractions. There was lack of split-dose recovery in NHEJ-deficient cells and DNA-PKcs inhibitor increased sensitivity to split-doses in glioma cells. Furthermore, siRNA knockdown of p53 in fibroblasts reduced split-dose recovery. In summary, cells defective in p53 are less sensitive to radiotherapy fraction size and lack of split-dose recovery in DNA ligase IV and DNA-PKcs mutant cells suggests the dependence of fraction size sensitivity on intact NHEJ.
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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.