ArticleScience advances2022
RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The trial behind it
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Who cites it
24 citing papers in PubMed, 47 citations in OpenAlex.
- Ribonucleotide Reductase Inhibition Triggers Ferroptosis in Genetically Defined Subsets of Non-Small Cell Lung Cancer.Cancer research communications · 2026Article
- Article
- 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
- Multiplexed TrAEL-seq captures DNA replication dynamics in mammalian cells.Nucleic acids research · 2026Article
- Pathway for the Development of ATR Inhibitors in Pediatric Malignancies: An ACCELERATE Multistakeholder Analysis.JCO precision oncology · 2026Review
- ENO1-mediated deoxycytidine synthesis and gemcitabine resistance by stabilizing RRM2 in pancreatic cancer.Cell death & disease · 2025Article
- Ribonucleotide reductase subunit M2 mediates the mTOR pathway to recruit furin endoprotease and promote maturation of dengue virus.iScience · 2025Article
- Synergistic inhibition of CHK1 and MUS81 to combat replication stress resistance in high-risk neuroblastoma.Scientific reports · 2025Article
- Low-amplitude copy number gains shape cancer through known and novel oncogenes with associated therapeutic vulnerabilities.Nucleic acids research · 2025Article
- ATR Inhibition Synergizes With Alkylating PI Polyamide Targeting MYCN by Suppressing DNA Repair in MYCN-Amplified Neuroblastoma.Cancer science · 2025Article
- Oxphos targeting ofFrontiers in oncology · 2025Article
- Cyclin Y interacts with Chk1 to activate RRM2/STAT3 signaling and promotes radioresistance in non-small cell lung cancer.International journal of biological sciences · 2025Article
- Synergistic machine learning models utilizing ferroptosis-related genes for improved neuroblastoma outcome prediction.Translational pediatrics · 2024Article
- Ribonucleotide reductase small subunit M2 promotes the proliferation of esophageal squamous cell carcinoma cellsActa pharmaceutica Sinica. B · 2024Article
- The potential of ribonucleotide reductase M2 as a novel prognostic maker and therapeutic target to inhibit medulloblastoma proliferation, migration, and invasiveness.Pediatric discovery · 2024Article
- Single cell sequencing of zebrafish kidney marrows reveals AHR2-dependent endogenous regulation of hematopoiesis.bioRxiv : the preprint server for biology · 2024Article
- A structure-based designed small molecule depletes hRpn13Nature communications · 2024Article
- Preclinical exploration of the DNA damage response pathway using the interactive neuroblastoma cell line explorer CLEAN.NAR cancer · 2024Article
- Targeting of RRM2 suppresses DNA damage response and activates apoptosis in atypical teratoid rhabdoid tumor.Journal of experimental & clinical cancer research : CR · 2023Article
Corrections and comments
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Authors and funding
42 authors at 7 institutions in 5 countries.
Funding
Abstract
High-risk neuroblastoma, a pediatric tumor originating from the sympathetic nervous system, has a low mutation load but highly recurrent somatic DNA copy number variants. Previously, segmental gains and/or amplifications allowed identification of drivers for neuroblastoma development. Using this approach, combined with gene dosage impact on expression and survival, we identified ribonucleotide reductase subunit M2 (RRM2) as a candidate dependency factor further supported by growth inhibition upon in vitro knockdown and accelerated tumor formation in a neuroblastoma zebrafish model coexpressing human RRM2 with MYCN. Forced RRM2 induction alleviates excessive replicative stress induced by CHK1 inhibition, while high RRM2 expression in human neuroblastomas correlates with high CHK1 activity. MYCN-driven zebrafish tumors with RRM2 co-overexpression exhibit differentially expressed DNA repair genes in keeping with enhanced ATR-CHK1 signaling activity. In vitro, RRM2 inhibition enhances intrinsic replication stress checkpoint addiction. Last, combinatorial RRM2-CHK1 inhibition acts synergistic in high-risk neuroblastoma cell lines and patient-derived xenograft models, illustrating the therapeutic potential.
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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.