ArticleOncotarget2015
The PARP inhibitor olaparib enhances the sensitivity of Ewing sarcoma to trabectedin.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 54 papers.
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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.
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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
54 citing papers in PubMed, 98 citations in OpenAlex.
- Precision oncology in the treatment of patients with bone sarcomas: an up-to-date narrative review.Exploration of targeted anti-tumor therapy · 2026Review
- New Approaches to Investigate Novel Agents in Ewing Sarcoma: A Report From the Children's Oncology Group Bone Tumor Committee.Pediatric blood & cancer · 2025Review
- Evaluation of Mithramycin in Combination with Chemotherapeutic Agents Against Ewing Sarcoma Cell Lines.Cancers · 2025Article
- Efficacy of NAMPT Inhibitors in Pancreatic Cancer After Stratification by MAP17 (PDZK1IP1) Levels.Cancers · 2025Article
- Exploiting divergent mechanisms of trabectedin for bone tumors.Molecular therapy. Oncology · 2025Article
- Trabectedin Induces Synthetic Lethality via the p53-Dependent Apoptotic Pathway in Ovarian Cancer Cells Without BRCA Mutations When Used in Combination with Niraparib.International journal of molecular sciences · 2025Article
- A Bayesian active learning platform for scalable combination drug screens.Nature communications · 2025Article
- Druggable upregulated proteins in EWS-FLI-driven Ewing sarcoma as emerging new therapeutic targets.American journal of translational research · 2025Review
- Xenografting Human Musculoskeletal Sarcomas in Mice, Chick Embryo, and Zebrafish: How to Boost Translational Research.Biomedicines · 2024Review
- Unlocking epigenetics for precision treatment of Ewing's sarcoma.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Review
- Trabectedin and Lurbinectedin Modulate the Interplay between Cells in the Tumour Microenvironment-Progresses in Their Use in Combined Cancer Therapy.Molecules (Basel, Switzerland) · 2024Review
- Attenuation of Tumor Burden in Response to Rucaparib in Lung Adenocarcinoma: The Contribution of Oxidative Stress, Apoptosis, and DNA Damage.International journal of molecular sciences · 2023Article
- Ewing sarcoma and related FET family translocation-associated round cell tumors: A century of clinical and scientific progress.Genes, chromosomes & cancer · 2022Article
- CRISPR/Cas9-Directed Gene Trap Constitutes a Selection System for CorrectedInternational journal of molecular sciences · 2022Article
- Management of Unresectable Localized Pelvic Bone Sarcomas: Current Practice and Future Perspectives.Cancers · 2022Review
- Article
- Review of various NAMPT inhibitors for the treatment of cancer.Frontiers in pharmacology · 2022Review
- Toxicological Properties of 7-Methylguanine, and Preliminary Data on its Anticancer Activity.Frontiers in pharmacology · 2022Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent preclinical evidence has suggested that Ewing Sarcoma (ES) bearing EWSR1-ETS fusions could be particularly sensitive to PARP inhibitors (PARPinh) in combination with DNA damage repair (DDR) agents. Trabectedin is an antitumoral agent that modulates EWSR1-FLI1 transcriptional functions, causing DNA damage. Interestingly, PARP1 is also a transcriptional regulator of EWSR1-FLI1, and PARPinh disrupts the DDR machinery. Thus, given the impact and apparent specificity of both agents with regard to the DNA damage/DDR system and EWSR1-FLI1 activity in ES, we decided to explore the activity of combining PARPinh and Trabectedin in in vitro and in vivo experiments. The combination of Olaparib and Trabectedin was found to be highly synergistic, inhibiting cell proliferation, inducing apoptosis, and the accumulation of G2/M. The drug combination also enhanced γH2AX intranuclear accumulation as a result of DNA damage induction, DNA fragmentation and global DDR deregulation, while EWSR1-FLI1 target expression remained unaffected. The effect of the drug combination was corroborated in a mouse xenograft model of ES and, more importantly, in two ES patient-derived xenograft (PDX) models in which the tumors showed complete regression. In conclusion, the combination of the two agents leads to a biologically significant deregulation of the DDR machinery that elicits relevant antitumor activity in preclinical models and might represent a promising therapeutic tool that should be further explored for translation to the clinical setting.
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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.