ArticleOncotarget2017
Inhibition of CHK1 sensitizes Ewing sarcoma cells to the ribonucleotide reductase inhibitor gemcitabine.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 39 citations in OpenAlex.
- DNA replication stress and translational repression converge to drive CDK1- and caspase-dependent apoptosis in Ewing sarcoma.Oncogene · 2026Article
- Combined Inhibition of ATR and Ribonucleotide Reductase Induces Synergistic Antineoplastic Activity in Osteosarcoma Cells.Cancer reports (Hoboken, N.J.) · 2026Article
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 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
- 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
- Arginine methylation regulates Ewing sarcoma cell viability in aFrontiers in oncology · 2025Article
- EWS-FLI1 and Activator Protein-1 (AP-1) Reciprocally Regulate Extracellular-Matrix Proteins in Ewing sarcoma Cells.International journal of molecular sciences · 2024Article
- Enhancing Standard of Care Chemotherapy Efficacy Using DNA-Dependent Protein Kinase (DNA-PK) Inhibition in Preclinical Models of Ewing Sarcoma.Molecular cancer therapeutics · 2024Article
- Review
- Revisiting 'Hallmarks of Cancer' In Sarcomas.Journal of Cancer · 2024Review
- 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
- Molecularly Defined Subsets of Ewing Sarcoma Tumors Differ in Their Responses to IGF1R and WEE1 Inhibition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- 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
- Novel Targeted Therapeutic Strategies for Ewing Sarcoma.Cancers · 2022Review
- CDC7 kinase (DDK) inhibition disrupts DNA replication leading to mitotic catastrophe in Ewing sarcoma.Cell death discovery · 2022Article
- Preclinical efficacy of prexasertib in acute lymphoblastic leukemia.British journal of haematology · 2021Article
- Translational evidence for RRM2 as a prognostic biomarker and therapeutic target in Ewing sarcoma.Molecular cancer · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Ewing sarcoma is a bone and soft tissue sarcoma that occurs in children and young adults. The EWS-FLI1 gene fusion is the driver mutation in most Ewing sarcoma tumors and functions, in part, as an aberrant transcription factor. We recently identified that Ewing sarcoma cells are sensitive to inhibition of ribonucleotide reductase (RNR), which catalyzes the formation of deoxyribonucleotides from ribonucleotides. In this report, we show that Ewing sarcoma cells are sensitive to treatment with clofarabine, which is a nucleoside analogue and allosteric inhibitor of RNR. However, clofarabine is a reversible inhibitor of RNR and we found that the effect of clofarabine is limited when using a short (6-hour) drug treatment. Gemcitabine, on the other hand, is an irreversible inhibitor of the RRM1 subunit of RNR and this drug induces apoptosis in Ewing sarcoma cells when used in both 6-hour and longer drug treatments. Treatment of Ewing sarcoma cells with gemcitabine also results in activation of checkpoint kinase 1 (CHK1), which is a critical mediator of cell survival in the setting of impaired DNA replication. Notably, inhibition of CHK1 function in Ewing sarcoma cells using a small-molecule CHK1 inhibitor, or siRNA knockdown, in combination with gemcitabine results in increased toxicity both
Indexed as
Identifiers
What OpenQuestion holds
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.