ArticleMolecular cancer therapeutics2013
RETRACTED: Combining PARP-1 inhibition and radiation in Ewing sarcoma results in lethal DNA damage.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 57 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 86 citations in OpenAlex.
- New Approaches to Investigate Novel Agents in Ewing Sarcoma: A Report From the Children's Oncology Group Bone Tumor Committee.Pediatric blood & cancer · 2025Review
- The Combination of PARP and Topoisomerase 1 Inhibitors Improves Radiation Therapy for Ewing Sarcoma.Cancer science · 2025Article
- Druggable upregulated proteins in EWS-FLI-driven Ewing sarcoma as emerging new therapeutic targets.American journal of translational research · 2025Review
- Retraction: Combining PARP-1 Inhibition and Radiation in Ewing Sarcoma Results in Lethal DNA Damage.Molecular cancer therapeutics · 2024Article
- Unlocking epigenetics for precision treatment of Ewing's sarcoma.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Review
- Novel modifications of PARP inhibitor veliparib increase PARP1 binding to DNA breaks.The Biochemical journal · 2024Article
- Poly(ADP-ribose) Polyremase-1 (PARP-1) Inhibition: A Promising Therapeutic Strategy for ETS-Expressing Tumours.International journal of molecular sciences · 2023Review
- Radiotherapy in bone sarcoma: the quest for better treatment option.BMC cancer · 2023Review
- Novel insights into biomarkers of progression in Desmoid tumor.Frontiers in oncology · 2023Review
- PARP-1: a critical regulator in radioprotection and radiotherapy-mechanisms, challenges, and therapeutic opportunities.Frontiers in pharmacology · 2023Review
- B-cell lymphoma 2 family members and sarcomas: a promising target in a heterogeneous disease.Exploration of targeted anti-tumor therapy · 2023Review
- Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer.Nature reviews. Cancer · 2022Review
- Management of Unresectable Localized Pelvic Bone Sarcomas: Current Practice and Future Perspectives.Cancers · 2022Review
- BRCA1-associated RING domain-1 (BARD1) loss and GBP1 expression enhance sensitivity to DNA damage in Ewing sarcoma.Cancer research communications · 2022Article
- Stat1 confers sensitivity to radiation in cervical cancer cells by controlling Parp1 levels: a new perspective for Parp1 inhibition.Cell death & disease · 2021Article
- Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model.British journal of cancer · 2021Article
- Exploiting Replication Stress as a Novel Therapeutic Intervention.Molecular cancer research : MCR · 2021Review
- Lysine Methyltransferase Inhibitors Impair H4K20me2 and 53BP1 Foci in Response to DNA Damage in Sarcomas, a Synthetic Lethality Strategy.Frontiers in cell and developmental biology · 2021Article
- Integrated Analysis of the Transcriptome Profile Reveals the Potential Roles Played by Long Noncoding RNAs in Immunotherapy for Sarcoma.Frontiers in oncology · 2021Article
Corrections and comments
- Retraction · 2024-11-04Concerns/Issues about Image · Duplication of/in Image ·
- Retracted
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Ewing sarcomas (ES) harbor a chromosomal translocation that fuses the EWS gene to an ETS transcription factor, most commonly Friend leukemia integration 1 (FLI1). The EWS-FLI1 fusion protein acts in a positive feedback loop to maintain the expression of PARP-1, which is involved in repair of DNA damage. Here, we examine the effects of PARP-1 inhibition and radiation therapy on Ewing sarcomas. In proliferation assays, the Ewing sarcoma cell lines RD-ES and SK-N-MC were much more sensitive than non-Ewing sarcoma cell lines to the PARP-1 inhibitor olaparib (Ola; IC50 0.5-1 μmol/L vs. >5 μmol/L) and to radiation (IC50 2-4 Gy vs. >6 Gy). PARP-1 inhibition with short hairpin RNA (shRNA) or Ola sensitized Ewing sarcoma cells, but not non-Ewing sarcoma cells, to radiation therapy in both proliferation and colony formation assays. Using the Comet assay, radiation of Ewing sarcoma cells with Ola, compared to without Ola, resulted in more DNA damage at 1 hour (mean tail moment 36-54 vs. 26-28) and sustained DNA damage at 24 hours (24-29 vs. 6-8). This DNA damage led to a 2.9- to 4.0-fold increase in apoptosis and a 1.6- to 2.4-fold increase in cell death. The effect of PARP-1 inhibition and radiation therapy on Ewing sarcoma cells was lost when EWS-FLI1 was silenced by shRNA. A small dose of radiation therapy (4 Gy), when combined with PARP-1 inhibition, stopped the growth of SK-N-MC flank tumors xenografts. In conclusion, PARP-1 inhibition in Ewing sarcomas amplifies the level and duration of DNA damage caused by radiation therapy, leading to synergistic increases in apoptosis and cell death in a EWS-FLI1-dependent manner.
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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.