2024
NAPRT Silencing in FH-Deficient Renal Cell Carcinoma Confers Therapeutic Vulnerabilities via NAD+ Depletion
Noronha K, Lucas K, Paradkar S, Edmonds J, Friedman S, Murray M, Liu S, Sajed D, Sachs C, Spurrier J, Raponi M, Liang J, Zeng H, Sundaram R, Shuch B, Vasquez J, Bindra R. NAPRT Silencing in FH-Deficient Renal Cell Carcinoma Confers Therapeutic Vulnerabilities via NAD+ Depletion. Molecular Cancer Research 2024, 22: of1-of16. PMID: 38949523, PMCID: PMC11445649, DOI: 10.1158/1541-7786.mcr-23-1003.Peer-Reviewed Original ResearchRenal cell carcinomaCellular processesCell carcinomaFumarate hydrataseImpact diverse cellular processesAlpha-ketoglutarate-dependent dioxygenasesDiverse cellular processesAccumulation of fumaratePreiss-Handler pathwayMultiple cellular processesLoss of function mutationsAssociated with silencingNicotinamide phosphoribosyl transferase inhibitorPattern of hypermethylationFH-deficient renal cell carcinomasSynergistic tumor cell killingAggressive subtype of renal cell carcinomaLoss of FHSubtype of renal cell carcinomaDNA repair processesPoly(ADP)-ribose polymerase inhibitorsCpG islandsTumor cell killingPreiss-HandlerCell line models
2019
PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma
Fons NR, Sundaram RK, Breuer GA, Peng S, McLean RL, Kalathil AN, Schmidt MS, Carvalho DM, Mackay A, Jones C, Carcaboso ÁM, Nazarian J, Berens ME, Brenner C, Bindra RS. PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma. Nature Communications 2019, 10: 3790. PMID: 31439867, PMCID: PMC6706443, DOI: 10.1038/s41467-019-11732-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBrain Stem NeoplasmsCell Line, TumorChildCytokinesDiffuse Intrinsic Pontine GliomaDNA MethylationEpigenetic RepressionFemaleGene Expression Regulation, NeoplasticHumansMiceNicotinamide PhosphoribosyltransferasePonsPrimary Cell CultureProtein Phosphatase 2CSynthetic Lethal MutationsXenograft Model Antitumor AssaysConceptsNicotinic acid phosphoribosyltransferaseSynthetic lethal interactionsNAMPT inhibitorsTumor-specific cell killingProtein phosphataseEpigenetic silencingMutant cellsKey genesCpG islandsLethal interactionsNAD biosynthesisGene expressionInhibitor sensitivityNAD metabolismOncogenic rolePediatric gliomasMutationsModel systemCell killingDriver mutationsPediatric high-grade gliomasMutant tumorsOncogenic driver mutationsNicotinamide phosphoribosyltransferase (NAMPT) inhibitionGenome