2018
Small molecule activators of protein phosphatase 2A for the treatment of castration-resistant prostate cancer.
McClinch K, Avelar R, Callejas D, Izadmehr S, Wiredja D, Perl A, Sangodkar J, Kastrinsky D, Schlatzer D, Cooper M, Kiselar J, Stachnik A, Yao S, Hoon D, McQuaid D, Zaware N, Gong Y, Brautigan D, Plymate S, Sprenger C, Oh W, Levine A, Kirschenbaum A, Sfakianos J, Sears R, DiFeo A, Ioannou Y, Ohlmeyer M, Narla G, Galsky M. Small molecule activators of protein phosphatase 2A for the treatment of castration-resistant prostate cancer. Cancer Research 2018, 78: canres.0123.2017. PMID: 29358171, PMCID: PMC5899650, DOI: 10.1158/0008-5472.can-17-0123.Peer-Reviewed Original ResearchConceptsCastrate-resistant prostate cancerAndrogen receptorProstate cancerCRPC cellsHuman castrate-resistant prostate cancerMultiple oncogenic signaling pathwaysSmall molecule activatorsAndrogen deprivation therapyAdvanced prostate cancerPrimary prostate cancerMurine xenograft modelGrowth inhibitory effectsDeprivation therapyCRPC treatmentTime-dependent mannerOncogenic signaling pathwaysPreclinical proofXenograft modelAR degradationCancer ResTumor suppressor PP2ATumor formationCancerAberrant reactivationSignaling pathways
2017
Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth
Sangodkar J, Perl A, Tohme R, Kiselar J, Kastrinsky D, Zaware N, Izadmehr S, Mazhar S, Wiredja D, O’Connor C, Hoon D, Dhawan N, Schlatzer D, Yao S, Leonard D, Borczuk A, Gokulrangan G, Wang L, Svenson E, Farrington C, Yuan E, Avelar R, Stachnik A, Smith B, Gidwani V, Giannini H, McQuaid D, McClinch K, Wang Z, Levine A, Sears R, Chen E, Duan Q, Datt M, Haider S, Ma’ayan A, DiFeo A, Sharma N, Galsky M, Brautigan D, Ioannou Y, Xu W, Chance M, Ohlmeyer M, Narla G. Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth. Journal Of Clinical Investigation 2017, 127: 2081-2090. PMID: 28504649, PMCID: PMC5451217, DOI: 10.1172/jci89548.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorCell SurvivalDrug Resistance, NeoplasmEnzyme ActivationEnzyme ActivatorsHumansMaleMice, Inbred BALB CMice, NudeMice, TransgenicProtein BindingProtein Phosphatase 2Proto-Oncogene Proteins p21(ras)Signal TransductionTumor BurdenXenograft Model Antitumor AssaysConceptsTumor suppressor proteinSmall molecule activatorsSuppressor proteinTumor suppressor protein phosphatase 2AMolecule activatorsProtein phosphatase 2AInactivation of kinasesOncogenic signaling proteinsPhosphatase 2AScaffold subunitSignaling proteinsEndogenous phosphatasesNegative regulatorOncogenic kinasesConformational changesCancer-associated molecular targetsKRAS-mutant lung cancerPP2AMolecular targetsProteinCancer cellsKinaseMouse xenograftsTreatment of cancerActivator