ArticleBMC cancer2020
Eltrombopag inhibits the proliferation of Ewing sarcoma cells via iron chelation and impaired DNA replication.
Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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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
10 citing papers in PubMed, 14 citations in OpenAlex.
- Identification of non-oncology drugs with activity against inflammatory and triple-negative breast cancer cell lines.Oncology letters · 2026Article
- Targeting GPX4 and FSP1 to exploit ferroptotic vulnerability in Ewing sarcoma.Frontiers in oncology · 2026Article
- SLFN11, far from being limited to responding to cancer DNA damage.Clinical and experimental medicine · 2025Review
- Histone Deacetylase Inhibitors Target DNA Replication Regulators and Replication Stress in Ewing Sarcoma Cells.Cancer research communications · 2025Article
- Auranofin and reactive oxygen species inhibit protein synthesis and regulate the level of the PLK1 protein in Ewing sarcoma cells.Frontiers in oncology · 2024Article
- Activator Protein-1 (AP-1) Signaling Inhibits the Growth of Ewing Sarcoma Cells in Response to DNA Replication Stress.Cancer research communications · 2023Article
- Emerging Roles of the Iron Chelators in Inflammation.International journal of molecular sciences · 2022Review
- Inhibitor of DNA binding 2 (ID2) regulates the expression of developmental genes and tumorigenesis in ewing sarcoma.Oncogene · 2022Article
- Eltrombopag increases the hematopoietic supporting ability of mesenchymal stem/stromal cells.Therapeutic advances in hematology · 2022Article
- Repurposing Eltrombopag as an Antimicrobial Agent Against Methicillin-ResistantFrontiers in microbiology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe treatment of Ewing sarcoma, an aggressive bone and soft tissue sarcoma, is associated with suboptimal outcomes and significant side-effects. Consequently, there is an urgent need to identify novel therapies that will improve outcomes for children and adults with Ewing sarcoma tumors while also decreasing treatment-related toxicities.
methodsWe analyzed data from the PRISM drug repurposing screen, which tested the activity of 4518 drugs across 578 cancer cell lines, to identify drugs that selectively inhibit the growth of Ewing sarcoma cell lines. We then tested the effects of a top hit from the screen on cell proliferation, cell cycle progression, and activation of the DNA damage pathway using Ewing sarcoma cell lines. We also used a CRISPR/Cas9 gene knockout approach to investigate the role of Schlafen 11 (SLFN11), a restriction factor for DNA replication stress that is overexpressed in Ewing sarcoma tumors, in mediating the sensitivity of Ewing sarcoma cells to the drug.
resultsWe found that eltrombopag, an FDA-approved thrombopoietin-receptor agonist (TPO-RA) that is currently being evaluated as a treatment for chemotherapy-induced thrombocytopenia, inhibits the growth of Ewing sarcoma cell lines in vitro in proliferation and colony formation assays. However, from a mechanistic standpoint, the thrombopoietin receptor is not expressed in Ewing sarcoma cells and we show that eltrombopag impairs DNA replication and causes DNA damage in Ewing sarcoma cells by chelating iron, a known "off-target" effect of the drug. We also found that the sensitivity of Ewing sarcoma cells to eltrombopag is mediated, in part, by SLFN11, which regulates the cellular response to DNA replication stress.
conclusionsEwing sarcoma cell lines are sensitive to eltrombopag and this drug could improve outcomes for patients with Ewing sarcoma tumors by both targeting the tumor, via chelation of iron and inhibition of DNA replication, and reducing chemotherapy-induced thrombocytopenia, via stimulation of the thrombopoietin receptor.
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Registered trials
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