ArticleThe Journal of clinical investigation2019
Single-dose radiotherapy disables tumor cell homologous recombination via ischemia/reperfusion injury.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04831983 (Single-Dose Image-Guided Radiotherapy), which is not on this map. Cited by 41 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.
Single-Dose Image-Guided Radiotherapy (IGRT) With Focal Boost to the MRI-defined Macroscopic Tumor Volume for Intermediate Unfavorable and High Risk Prostate Cancer
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Treatment progress of spinal metastatic cancer: a powerful tool for improving the quality of life of the patients.Journal of orthopaedic surgery and research · 2023Pooled it
- Phase 3 Multi-Center, Prospective, Randomized Trial Comparing Single-Dose 24 Gy Radiation Therapy to a 3-Fraction SBRT Regimen in the Treatment of Oligometastatic Cancer.International journal of radiation oncology, biology, physics · 2021Trial
- Conformal Avoidance of Normal Organs at Risk by Perfusion-Modulated Dose Sculpting in Tumor Single-Dose Radiation Therapy.International journal of radiation oncology, biology, physics · 2021Trial
- Enhancing gemcitabine uptake by promoting dimerization of ENT1 transporter improves response rates of patients with sarcoma.The Journal of clinical investigation · 2026Article
- The transformative role of SBRT in the management of spinal metastases.Nature reviews. Clinical oncology · 2026Review
- Article
- The impact of CHEK2 status on radiosurgical outcomes in breast cancer brain metastases.Neurosurgical review · 2026Article
- Correction and utilization of the washout effect in range-verification PET for particle therapy.Radiological physics and technology · 2026Review
- Historical Review of the Role of Indirect Cell Death in High-Dose Per Fraction Radiation Therapy.Advances in radiation oncology · 2026Review
- Cancer Immunotherapy in Combination with Radiotherapy and/or Chemotherapy: Mechanisms and Clinical Therapy.MedComm · 2025Review
- Radiosensitizing the SUMO stress response intensifies single-dose radiotherapy tumor cure.JCI insight · 2025Article
- The Proimmunomodulatory and Anti-immunomodulatory Effects of Radiotherapy in Oncologic Care.Hematology/oncology clinics of North America · 2025Review
- Single-Dose Radiation Therapy for Localized Prostate Cancer: Where Does the Evidence Lead?Cancers · 2025Review
- Emerging roles of the acid sphingomyelinase/ceramide pathway in metabolic and cardiovascular diseases: Mechanistic insights and therapeutic implications.World journal of cardiology · 2025Review
- Image-guided treatment of mouse tumours with radioactive ion beams.Nature physics · 2025Article
- Synthetic reprogramming of tumor cell fate for modulating radiotherapy-induced dynamic responses: perspectives on radiosensitizing and immunoregulatory effects.Theranostics · 2025Review
- Improving radiation therapy efficacy considering DNA repair, TP53 mutations, microscopic heterogeneity, and low- and high-dose apoptosis.Frontiers in oncology · 2025Review
- Article
- Lesion Dosimetry for [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2023Article
- Novel unconventional radiotherapy techniques: Current status and future perspectives - Report from the 2nd international radiation oncology online seminar.Clinical and translational radiation oncology · 2023Article
Corrections and comments
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Authors and funding
31 authors at 5 institutions in 2 countries.
Funding
Abstract
Tumor cure with conventional fractionated radiotherapy is 65%, dependent on tumor cell-autonomous gradual buildup of DNA double-strand break (DSB) misrepair. Here we report that single-dose radiotherapy (SDRT), a disruptive technique that ablates more than 90% of human cancers, operates a distinct dual-target mechanism, linking acid sphingomyelinase-mediated (ASMase-mediated) microvascular perfusion defects to DNA unrepair in tumor cells to confer tumor cell lethality. ASMase-mediated microcirculatory vasoconstriction after SDRT conferred an ischemic stress response within parenchymal tumor cells, with ROS triggering the evolutionarily conserved SUMO stress response, specifically depleting chromatin-associated free SUMO3. Whereas SUMO3, but not SUMO2, was indispensable for homology-directed repair (HDR) of DSBs, HDR loss of function after SDRT yielded DSB unrepair, chromosomal aberrations, and tumor clonogen demise. Vasoconstriction blockade with the endothelin-1 inhibitor BQ-123, or ROS scavenging after SDRT using peroxiredoxin-6 overexpression or the SOD mimetic tempol, prevented chromatin SUMO3 depletion, HDR loss of function, and SDRT tumor ablation. We also provide evidence of mouse-to-human translation of this biology in a randomized clinical trial, showing that 24 Gy SDRT, but not 3×9 Gy fractionation, coupled early tumor ischemia/reperfusion to human cancer ablation. The SDRT biology provides opportunities for mechanism-based selective tumor radiosensitization via accessing of SDRT/ASMase signaling, as current studies indicate that this pathway is tractable to pharmacologic intervention.
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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.