Matches in SemOpenAlex for { <https://semopenalex.org/work/W4285385872> ?p ?o ?g. }
- W4285385872 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." @default.
- W4285385872 created "2022-07-14" @default.
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- W4285385872 date "2022-07-15" @default.
- W4285385872 modified "2023-10-11" @default.
- W4285385872 title "RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition" @default.
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- W4285385872 cites W2168459422 @default.
- W4285385872 cites W2169484696 @default.
- W4285385872 cites W2171129793 @default.
- W4285385872 cites W2181205541 @default.
- W4285385872 cites W2201544449 @default.
- W4285385872 cites W2317828408 @default.
- W4285385872 cites W2330148258 @default.
- W4285385872 cites W2425235023 @default.
- W4285385872 cites W2526176724 @default.
- W4285385872 cites W2531499154 @default.
- W4285385872 cites W2540036007 @default.
- W4285385872 cites W2546675038 @default.
- W4285385872 cites W2551596349 @default.
- W4285385872 cites W2555542859 @default.
- W4285385872 cites W2592185869 @default.
- W4285385872 cites W2604986078 @default.
- W4285385872 cites W2702680930 @default.
- W4285385872 cites W2741613334 @default.
- W4285385872 cites W2745330422 @default.
- W4285385872 cites W2778721681 @default.
- W4285385872 cites W2788562722 @default.
- W4285385872 cites W2799540870 @default.
- W4285385872 cites W2801382830 @default.
- W4285385872 cites W2803554589 @default.