ArticleJournal of experimental & clinical cancer research : CR2023
Targeting of RRM2 suppresses DNA damage response and activates apoptosis in atypical teratoid rhabdoid tumor.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- The future of targeted therapies for pediatric central nervous system tumors.Neuro-oncology advances · 2026Review
- Targeting endosomal trafficking-mediated antigen escape to resensitize myeloma to CAR-T therapy.Journal for immunotherapy of cancer · 2026Article
- Targeting replication stress in neuroblastoma by exploiting the synergistic potential of second generation RRM2 and CHK1 inhibitors.Cell death & disease · 2026Article
- ENO1-mediated deoxycytidine synthesis and gemcitabine resistance by stabilizing RRM2 in pancreatic cancer.Cell death & disease · 2025Article
- Targeting E2F8 sensitizes gemcitabine-resistant gallbladder cancer to PARP inhibitors by disrupting RRM2-driven DNA repair.Journal of experimental & clinical cancer research : CR · 2025Article
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- DEAD/H-box RNA helicase 10 promotes pancreatic cancer cell proliferationWorld journal of gastrointestinal oncology · 2025Article
- KAT7-acetylated YBX1 promotes hepatocellular carcinoma proliferation by reprogramming nucleotide metabolism.BMC cancer · 2025Article
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- A glutamine metabolish-associated prognostic model to predict prognosis and therapeutic responses of hepatocellular carcinoma.Biology direct · 2024Article
- LncOCMRL1 promotes oral squamous cell carcinoma growth and metastasis via the RRM2/EMT pathway.Journal of experimental & clinical cancer research : CR · 2024Article
- High RRM2 Correlates with Mitochondrial and Immune Responses in the Eosinophilic Subtype of Clear Cell Renal Cell Carcinoma.Journal of inflammation research · 2024Article
- Multi-Omic Analysis of Glioma Identifies RRM2 as a Prognostic Biomarker Associated With Tumor Stemness and Cell Cycle-Related Pathways.Technology in cancer research & treatmentArticle
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Authors and funding
15 authors at 8 institutions in 2 countries.
Funding
Abstract
backgroundAtypical teratoid rhabdoid tumors (ATRT) is a rare but aggressive malignancy in the central nervous system, predominantly occurring in early childhood. Despite aggressive treatment, the prognosis of ATRT patients remains poor. RRM2, a subunit of ribonucleotide reductase, has been reported as a biomarker for aggressiveness and poor prognostic conditions in several cancers. However, little is known about the role of RRM2 in ATRT. Uncovering the role of RRM2 in ATRT will further promote the development of feasible strategies and effective drugs to treat ATRT.
methodsExpression of RRM2 was evaluated by molecular profiling analysis and was confirmed by IHC in both ATRT patients and PDX tissues. Follow-up in vitro studies used shRNA knockdown RRM2 in three different ATRT cells to elucidate the oncogenic role of RRM2. The efficacy of COH29, an RRM2 inhibitor, was assessed in vitro and in vivo. Western blot and RNA-sequencing were used to determine the mechanisms of RRM2 transcriptional activation in ATRT.
resultsRRM2 was found to be significantly overexpressed in multiple independent ATRT clinical cohorts through comprehensive bioinformatics and clinical data analysis in this study. The expression level of RRM2 was strongly correlated with poor survival rates in patients. In addition, we employed shRNAs to silence RRM2, which led to significantly decrease in ATRT colony formation, cell proliferation, and migration. In vitro experiments showed that treatment with COH29 resulted in similar but more pronounced inhibitory effect. Therefore, ATRT orthotopic mouse model was utilized to validate this finding, and COH29 treatment showed significant tumor growth suppression and prolong overall survival. Moreover, we provide evidence that COH29 treatment led to genomic instability, suppressed homologous recombinant DNA damage repair, and subsequently induced ATRT cell death through apoptosis in ATRT cells.
conclusionsCollectively, our study uncovers the oncogenic functions of RRM2 in ATRT cell lines, and highlights the therapeutic potential of targeting RRM2 in ATRT. The promising effect of COH29 on ATRT suggests its potential suitability for clinical trials as a novel therapeutic approach for ATRT.
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