ArticleOncotarget2017
EWS-FLI1 confers exquisite sensitivity to NAMPT inhibition in Ewing sarcoma cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The trial behind it
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- NAPRT Expression and Epigenetic Regulation in Pediatric Rhabdomyosarcoma as a Potential Biomarker for NAMPT Inhibition.Molecular cancer therapeutics · 2026Article
- Integrated Workflow for Drug Repurposing in Glioblastoma: Computational Prediction and Preclinical Validation of Therapeutic Candidates.Brain sciences · 2025Article
- Mechanisms of resistance to NAMPT inhibitors in cancer.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Article
- Enhancing Standard of Care Chemotherapy Efficacy Using DNA-Dependent Protein Kinase (DNA-PK) Inhibition in Preclinical Models of Ewing Sarcoma.Molecular cancer therapeutics · 2024Article
- Inhibition of NAD+-Dependent Metabolic Processes Induces Cellular Necrosis and Tumor Regression in Rhabdomyosarcoma Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Article
- Review of various NAMPT inhibitors for the treatment of cancer.Frontiers in pharmacology · 2022Review
- One oncogene, several vulnerabilities: EWS/FLI targeted therapies for Ewing sarcoma.Journal of bone oncology · 2021Article
- Targeting the NAD Salvage Synthesis Pathway as a Novel Therapeutic Strategy for Osteosarcomas with Low NAPRT Expression.International journal of molecular sciences · 2021Article
- p21-activated kinases as viable therapeutic targets for the treatment of high-risk Ewing sarcoma.Oncogene · 2021Article
- Discovery of novel candidates for anti-liposarcoma therapies by medium-scale high-throughput drug screening.PloS one · 2021Article
- NADSignal transduction and targeted therapy · 2021Review
- Article
- Targeting Glycolysis through Inhibition of Lactate Dehydrogenase Impairs Tumor Growth in Preclinical Models of Ewing Sarcoma.Cancer research · 2019Article
- Beyond Energy Metabolism: Exploiting the Additional Roles of NAMPT for Cancer Therapy.Frontiers in oncology · 2019Review
- FK866 inhibits the epithelial-mesenchymal transition of hepatocarcinoma MHCC97-H cells.Oncology letters · 2018Article
- Identifying the druggable interactome of EWS-FLI1 reveals MCL-1 dependent differential sensitivities of Ewing sarcoma cells to apoptosis inducers.Oncotarget · 2018Article
- Matrix Screen Identifies Synergistic Combination of PARP Inhibitors and Nicotinamide Phosphoribosyltransferase (NAMPT) Inhibitors in Ewing Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- EWS/FLI is a Master Regulator of Metabolic Reprogramming in Ewing Sarcoma.Molecular cancer research : MCR · 2017Article
Corrections and comments
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Authors and funding
13 authors at 8 institutions in 3 countries.
Funding
Abstract
Ewing sarcoma (EwS) is the second most common bone cancer in children and adolescents with a high metastatic potential. EwS development is driven by a specific chromosomal translocation resulting in the generation of a chimeric EWS-ETS transcription factor, most frequently EWS-FLI1.Nicotinamide adenine dinucleotide (NAD) is a key metabolite of energy metabolism involved in cellular redox reactions, DNA repair, and in the maintenance of genomic stability. This study describes targeting nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD synthesis, by FK866 in EwS cells. Here we report that blocking NAMPT leads to exhaustive NAD depletion in EwS cells, followed by a metabolic collapse and cell death. Using conditional EWS-FLI1 knockdown by doxycycline-inducible shRNA revealed that EWS-FLI1 depletion significantly reduces the sensitivity of EwS cells to NAMPT inhibition. Consistent with this finding, a comparison of 7 EwS cell lines of different genotypes with 5 Non-EwS cell lines and mesenchymal stem cells revealed significantly higher FK866 sensitivity of EWS-ETS positive EwS cells, with IC50 values mostly below 1nM.Taken together, our data reveal evidence of an important role of the NAMPT-mediated NAD salvage pathway in the energy homeostasis of EwS cells and suggest NAMPT inhibition as a potential new treatment approach for 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.