ArticleJournal of cancer research and clinical oncology2023
Synergistic anticancer activity of combined ATR and ribonucleotide reductase inhibition in Ewing's sarcoma cells.
Article in Journal of cancer research and clinical oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 12 citations in OpenAlex.
- DNA replication stress and translational repression converge to drive CDK1- and caspase-dependent apoptosis in Ewing sarcoma.Oncogene · 2026Article
- Autophagy impairs the sensitivity of Ewing sarcoma cells to PARP inhibitors.Cancer chemotherapy and pharmacology · 2026Article
- Combined Inhibition of ATR and Ribonucleotide Reductase Induces Synergistic Antineoplastic Activity in Osteosarcoma Cells.Cancer reports (Hoboken, N.J.) · 2026Article
- TH-302 (evofosfamide) monotherapy exerts anticancer activity in Ewing's sarcoma cells under hypoxia.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- The Puzzle of Genetic Stability and Chromosomal Copy Number Alterations for the Therapy of Ewing Sarcoma.Cancers · 2025Review
- New Approaches to Investigate Novel Agents in Ewing Sarcoma: A Report From the Children's Oncology Group Bone Tumor Committee.Pediatric blood & cancer · 2025Review
- Clinical application of targeted α-emitter therapy in gastroenteropancreatic neuroendocrine neoplasms.Journal of gastroenterology · 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
- Enhancing Standard of Care Chemotherapy Efficacy Using DNA-Dependent Protein Kinase (DNA-PK) Inhibition in Preclinical Models of Ewing Sarcoma.Molecular cancer therapeutics · 2024Article
- Stemness and Cell Cycle Regulators and Their Modulation by Retinoic Acid in Ewing Sarcoma.Current issues in molecular biology · 2024Article
- Review
- Synergistic induction of apoptosis in liver cancer cells: exploring the combined potential of doxorubicin and XL-888.Medical oncology (Northwood, London, England) · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeEwing's sarcoma is a highly malignant childhood tumour whose outcome has hardly changed over the past two decades despite numerous attempts at chemotherapy intensification. It is therefore essential to identify new treatment options. The present study was conducted to explore the effectiveness of combined inhibition of two promising targets, ATR and ribonucleotide reductase (RNR), in Ewing's sarcoma cells.
methodsEffects of the ATR inhibitor VE821 in combination with the RNR inhibitors triapine and didox were assessed in three Ewing's sarcoma cell lines with different TP53 status (WE-68, SK-ES-1, A673) by flow cytometric analysis of cell death, mitochondrial depolarisation and cell cycle distribution as well as by caspase 3/7 activity determination, by immunoblotting and by real-time RT-PCR. Interactions between inhibitors were evaluated by combination index analysis.
resultsSingle ATR or RNR inhibitor treatment produced small to moderate effects, while their combined treatment produced strong synergistic ones. ATR and RNR inhibitors elicited synergistic cell death and cooperated in inducing mitochondrial depolarisation, caspase 3/7 activity and DNA fragmentation, evidencing an apoptotic form of cell death. All effects were independent of functional p53. In addition, VE821 in combination with triapine increased p53 level and induced p53 target gene expression (CDKN1A, BBC3) in p53 wild-type Ewing's sarcoma cells.
conclusionOur study reveals that combined targeting of ATR and RNR was effective against Ewing's sarcoma in vitro and thus rationalises an in vivo exploration into the potential of combining ATR and RNR inhibitors as a new strategy for the treatment of this challenging disease.
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