2022
The driver role of JAK‐STAT signalling in cancer stemness capabilities leading to new therapeutic strategies for therapy‐ and castration‐resistant prostate cancer
Lo U, Chen Y, Cen J, Deng S, Luo J, Zhau H, Ho L, Lai C, Mu P, Chung L, Hsieh J. The driver role of JAK‐STAT signalling in cancer stemness capabilities leading to new therapeutic strategies for therapy‐ and castration‐resistant prostate cancer. Clinical And Translational Medicine 2022, 12: e978. PMID: 35908276, PMCID: PMC9339240, DOI: 10.1002/ctm2.978.Peer-Reviewed Original ResearchConceptsCastration-resistant prostate cancerProstate cancerCancer stem cellsActivation of JAKJAK-STAT signalingGene set enrichment analysisJAK-STAT1 pathwaySTAT1 inhibitorAcquisition of stemness propertiesProstate cancer cell linesProstate cancer stemnessAssociated with cancer stem cellsIn vivo anti-tumor activityMetastatic prostate cancerTumor-initiating capabilityJAK-STATProstasphere assayDownstream effectorsIngenuity PathwayGenetic manipulationCSC genesBioinformatics analysisEnrichment analysisJAK-STAT1Signaling pathway
2020
Abstract NG06: CHD1-loss confers AR targeted therapy resistance via promoting cancer heterogeneity and lineage plasticity
Zhang Z, Zhou C, Li X, Barnes S, Deng S, Hoover E, Chen C, Lee Y, Wang C, Tirado C, Metang L, Johnson N, Wongvipat J, Navrazhina K, Cao Z, Abida W, Lujambio A, Li S, Malladi V, Sawyers C, Mu P. Abstract NG06: CHD1-loss confers AR targeted therapy resistance via promoting cancer heterogeneity and lineage plasticity. Cancer Research 2020, 80: ng06-ng06. DOI: 10.1158/1538-7445.am2020-ng06.Peer-Reviewed Original ResearchMetastatic prostate cancerLineage plasticityAndrogen receptorResistance to ARShort hairpin RNAEpithelial to mesenchymal transitionChromodomain helicase DNA-binding protein 1Genomic alterationsCHD1 lossCancer heterogeneityProstate cancerClinical successTumor cellsLuminal prostate epithelial cellsProstate cancer cell line modelsWeeks of xenograftingTargetable driver mutationsCancer cell line modelsResistance to enzalutamideAR target genesProstate epithelial cellsProstate tumor cellsHuman prostate cancerProstate cancer heterogeneityAmerican Association for Cancer ResearchLoss of CHD1 Promotes Heterogeneous Mechanisms of Resistance to AR-Targeted Therapy via Chromatin Dysregulation
Zhang Z, Zhou C, Li X, Barnes S, Deng S, Hoover E, Chen C, Lee Y, Zhang Y, Wang C, Metang L, Wu C, Tirado C, Johnson N, Wongvipat J, Navrazhina K, Cao Z, Choi D, Huang C, Linton E, Chen X, Liang Y, Mason C, de Stanchina E, Abida W, Lujambio A, Li S, Lowe S, Mendell J, Malladi V, Sawyers C, Mu P. Loss of CHD1 Promotes Heterogeneous Mechanisms of Resistance to AR-Targeted Therapy via Chromatin Dysregulation. Cancer Cell 2020, 37: 584-598.e11. PMID: 32220301, PMCID: PMC7292228, DOI: 10.1016/j.ccell.2020.03.001.Peer-Reviewed Original ResearchMeSH KeywordsAndrogen AntagonistsAnimalsApoptosisBiomarkers, TumorCell ProliferationChromatinDNA HelicasesDNA-Binding ProteinsDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHigh-Throughput Screening AssaysHumansMaleMiceProstatic Neoplasms, Castration-ResistantReceptors, AndrogenRNA, Small InterferingTranscription FactorsTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsAntiandrogen resistanceChromatin dysregulationCHD1 lossProstate cancerGenomic copy number alterationsRNA-seq analysisResistance to hormonal therapyCopy number alterationsAR-targeted therapiesMetastatic prostate cancerATAC-seqClosed chromatinRNA-seqTranscriptional plasticityTranscription factorsFunctional screeningTranscriptomic changesMechanisms of resistanceHormone therapyLineage programsChromatinCHD1Global changeIntegrated analysisTherapy