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• W2514410552 abstract "// Kelli L. Goss 1 and David J. Gordon 1 1 Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Iowa, Iowa City, Iowa, USA Correspondence to: David J. Gordon, email: // Keywords : Ewing sarcoma, ribonucleotide reductase, ciclopirox, iron chelator Received : June 28, 2016 Accepted : August 13, 2016 Published : August 19, 2016 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." @default.
• W2514410552 created "2016-09-16" @default.
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• W2514410552 date "2016-08-19" @default.
• W2514410552 modified "2023-09-25" @default.
• W2514410552 title "Gene expression signature based screening identifies ribonucleotide reductase as a candidate therapeutic target in Ewing sarcoma" @default.
• W2514410552 cites W1514606780 @default.
• W2514410552 cites W1560585642 @default.
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• W2514410552 cites W1840981240 @default.
• W2514410552 cites W1971516612 @default.
• W2514410552 cites W1972623885 @default.
• W2514410552 cites W1973109316 @default.
• W2514410552 cites W1974216923 @default.
• W2514410552 cites W1982606752 @default.
• W2514410552 cites W1986462630 @default.
• W2514410552 cites W1995580021 @default.
• W2514410552 cites W2004212955 @default.
• W2514410552 cites W2007438323 @default.
• W2514410552 cites W2010201645 @default.
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• W2514410552 doi "https://doi.org/10.18632/oncotarget.11416" @default.
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