ArticleOncotarget2016
Gene expression signature based screening identifies ribonucleotide reductase as a candidate therapeutic target in Ewing sarcoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 45 citations in OpenAlex.
- Targeted and molecular therapies in Ewing sarcoma: a comprehensive review of preclinical and clinical advances.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- DNA replication stress and translational repression converge to drive CDK1- and caspase-dependent apoptosis in Ewing sarcoma.Oncogene · 2026Article
- Targeting GPX4 and FSP1 to exploit ferroptotic vulnerability in Ewing sarcoma.Frontiers in oncology · 2026Article
- Histone Deacetylase Inhibitors Target DNA Replication Regulators and Replication Stress in Ewing Sarcoma Cells.Cancer research communications · 2025Article
- Combined inhibition of ribonucleotide reductase and WEE1 induces synergistic anticancer activity in Ewing's sarcoma cells.BMC cancer · 2025Article
- Article
- EWS-FLI1 and Activator Protein-1 (AP-1) Reciprocally Regulate Extracellular-Matrix Proteins in Ewing sarcoma Cells.International journal of molecular sciences · 2024Article
- Auranofin and reactive oxygen species inhibit protein synthesis and regulate the level of the PLK1 protein in Ewing sarcoma cells.Frontiers in oncology · 2024Article
- Synergistic anticancer activity of combined ATR and ribonucleotide reductase inhibition in Ewing's sarcoma cells.Journal of cancer research and clinical oncology · 2023Article
- Activator Protein-1 (AP-1) Signaling Inhibits the Growth of Ewing Sarcoma Cells in Response to DNA Replication Stress.Cancer research communications · 2023Article
- TAS1553, a small molecule subunit interaction inhibitor of ribonucleotide reductase, exhibits antitumor activity by causing DNA replication stress.Communications biology · 2022Article
- WEE1 inhibition augments CDC7 (DDK) inhibitor-induced cell death in Ewing sarcoma by forcing premature mitotic entry and mitotic catastrophe.Cancer research communications · 2022Article
- Inhibitor of DNA binding 2 (ID2) regulates the expression of developmental genes and tumorigenesis in ewing sarcoma.Oncogene · 2022Article
- A Novel Defined Hypoxia-Related Gene Signature for Prognostic Prediction of Patients With Ewing Sarcoma.Frontiers in genetics · 2022Article
- Identification of aberrantly methylated-differentially expressed genes and potential agents for Ewing sarcoma.Annals of translational medicine · 2021Article
- Translational evidence for RRM2 as a prognostic biomarker and therapeutic target in Ewing sarcoma.Molecular cancer · 2021Article
- Fosciclopirox suppresses growth of high-grade urothelial cancer by targeting the γ-secretase complex.Cell death & disease · 2021Article
- Exploiting Replication Stress as a Novel Therapeutic Intervention.Molecular cancer research : MCR · 2021Review
- Reposition of the Fungicide Ciclopirox for Cancer Treatment.Recent patents on anti-cancer drug discovery · 2021Review
- The translational repressor 4E-BP1 regulates RRM2 levels and functions as a tumor suppressor in Ewing sarcoma tumors.Oncogene · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
There is a critical need in cancer therapeutics to identify targeted therapies that will improve outcomes and decrease toxicities compared to conventional, cytotoxic chemotherapy. Ewing sarcoma is a highly aggressive bone and soft tissue cancer that is caused by the EWS-FLI1 fusion protein. Although EWS-FLI1 is specific for cancer cells, and required for tumorigenesis, directly targeting this transcription factor has proven challenging. Consequently, targeting unique dependencies or key downstream mediators of EWS-FLI1 represent important alternative strategies. We used gene expression data derived from a genetically defined model of Ewing sarcoma to interrogate the Connectivity Map and identify a class of drugs, iron chelators, that downregulate a significant number of EWS-FLI1 target genes. We then identified ribonucleotide reductase M2 (RRM2), the iron-dependent subunit of ribonucleotide reductase (RNR), as one mediator of iron chelator toxicity in Ewing sarcoma cells. Inhibition of RNR in Ewing sarcoma cells caused apoptosis in vitro and attenuated tumor growth in an in vivo, xenograft model. Additionally, we discovered that the sensitivity of Ewing sarcoma cells to inhibition or suppression of RNR is mediated, in part, by high levels of SLFN11, a protein that sensitizes cells to DNA damage. This work demonstrates a unique dependency of Ewing sarcoma cells on RNR and supports further investigation of RNR inhibitors, which are currently used in clinical practice, as a novel approach for treating Ewing sarcoma.
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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.