2024
Exploiting Metabolic Defects in Glioma with Nanoparticle-Encapsulated NAMPT Inhibitors
Murray M, Noronha K, Wang Y, Friedman A, Paradkar S, Suh H, Sundaram R, Brenner C, Saltzman W, Bindra R. Exploiting Metabolic Defects in Glioma with Nanoparticle-Encapsulated NAMPT Inhibitors. Molecular Cancer Therapeutics 2024, 23: 1176-1187. PMID: 38691846, PMCID: PMC11292319, DOI: 10.1158/1535-7163.mct-24-0012.Peer-Reviewed Original ResearchConvection-enhanced deliveryCentral nervous systemTreatment of primary central nervous systemPrimary central nervous systemSustained drug release in vitroTumor growth delayAssociated with lower survival ratesBone marrow suppressionComplex mutational profilesNAMPT inhibitorsRelease in vitroIntracranial GBM xenograftsBlood-brain barrierDrug release in vitroRetinal toxicityMarrow suppressionNAMPTiGrowth delayTherapeutic vulnerabilitiesExtended survivalLow survival rateGBM xenograftsMutation profilesPromoter methylationAnticancer activity in vitro
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