Featured Publications
ZNF397 Deficiency Triggers TET2-driven Lineage Plasticity and AR-Targeted Therapy Resistance in Prostate Cancer
Xu Y, Yang Y, Wang Z, Sjostrom M, Jiang Y, Tang Y, Cheng S, Deng S, Wang C, Gonzalez J, Johnson N, Li X, Li X, Metang L, Mukherji A, Xu Q, Tirado C, Wainwright G, Yu X, Barnes S, Hofstad M, Chen Y, Zhu H, Hanker A, Raj G, Zhu G, He H, Wang Z, Arteaga C, Liang H, Feng F, Wang Y, Wang T, Mu P. ZNF397 Deficiency Triggers TET2-driven Lineage Plasticity and AR-Targeted Therapy Resistance in Prostate Cancer. Cancer Discovery 2024, 14: 1496-1521. PMID: 38591846, PMCID: PMC11285331, DOI: 10.1158/2159-8290.cd-23-0539.Peer-Reviewed Original ResearchConceptsLineage plasticityTherapy resistanceProstate cancerCancer cellsAndrogen receptorResistance to AR-targeted therapiesLuminal lineageAR-targeted therapiesOvercome therapy resistanceTransition of cancer cellsEpigenetic regulatory machineryBona fide coactivatorTherapy responseAR signalingEpigenetic rewiringDrug resistanceTherapeutic strategiesEpigenetic reprogrammingProstateTherapyCancerPhenotypic plasticityRegulatory machineryAndrogenTranscriptional programsLoss 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
2023
The Critical Interplay of CAF Plasticity and Resistance in Prostate Cancer.
Li X, Mu P. The Critical Interplay of CAF Plasticity and Resistance in Prostate Cancer. Cancer Research 2023, 83: 2990-2992. PMID: 37504898, DOI: 10.1158/0008-5472.can-23-2260.Commentaries, Editorials and LettersConceptsCastration-resistant prostate cancerAndrogen deprivation therapyProstate cancerAndrogen receptorCastration-resistant prostate cancer developmentDevelopment of castration-resistant prostate cancerGenetically engineered mouse modelsMyofibroblastic cancer-associated fibroblastsOvercome treatment resistanceCancer-associated fibroblastsIncreased tumor heterogeneityDeprivation therapyCRPC developmentProstate tumorsTumor microenvironmentLineage plasticityTreatment resistanceStromal compartmentStandard treatmentTumor heterogeneityCancer recurrenceDrug resistanceDisease progressionMouse modelSingle-cell RNA sequencing
2021
Overcoming oncogene addiction in breast and prostate cancers: a comparative mechanistic overview.
Blatt E, Kopplin N, Kumar S, Mu P, Conzen S, Raj G. Overcoming oncogene addiction in breast and prostate cancers: a comparative mechanistic overview. Endocrine Related Cancer 2021, 28: r31-r46. PMID: 33263560, PMCID: PMC8218927, DOI: 10.1530/erc-20-0272.Peer-Reviewed Original ResearchMeSH KeywordsBreastBreast NeoplasmsDrug Resistance, NeoplasmHumansMaleOncogene AddictionProstatic NeoplasmsReceptors, AndrogenReceptors, EstrogenConceptsProstate cancerHormone-dependent cancersBreast cancerTherapy resistanceAndrogen receptorMechanisms of endocrine therapy resistanceTherapeutic strategiesTherapy-resistant prostate cancerEndocrine therapy resistanceAdvanced prostate cancerTherapy-resistant tumorsNuclear receptorsMechanisms of resistancePotential therapeutic strategyEndocrine therapyMetastatic patientsAntiestrogen resistanceOncogene addictionClinical benefitTumor typesEstrogen receptorFrequent mechanismCancerReceptorsAugmented activity
2020
Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer
Zhang Z, Karthaus W, Lee Y, Gao V, Wu C, Russo J, Liu M, Mota J, Abida W, Linton E, Lee E, Barnes S, Chen H, Mao N, Wongvipat J, Choi D, Chen X, Zhao H, Manova-Todorova K, de Stanchina E, Taplin M, Balk S, Rathkopf D, Gopalan A, Carver B, Mu P, Jiang X, Watson P, Sawyers C. Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer. Cancer Cell 2020, 38: 279-296.e9. PMID: 32679108, PMCID: PMC7472556, DOI: 10.1016/j.ccell.2020.06.005.Peer-Reviewed Original ResearchMeSH KeywordsAndrogen AntagonistsAnimalsCancer-Associated FibroblastsCell Line, TumorCell ProliferationCells, CulturedDrug Resistance, NeoplasmGene Expression ProfilingGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMaleMice, SCIDNeuregulin-1Prostatic NeoplasmsTumor MicroenvironmentXenograft Model Antitumor AssaysConceptsCancer-associated fibroblastsProstate cancerAntiandrogen resistanceNeuregulin-1Second-generation antiandrogen therapyResistance to hormonal therapyCastration-resistant prostate cancerTreat advanced prostate cancerProstate organoid culturesSecond-generation antiandrogensAdvanced prostate cancerActivation of HER3Antiandrogen therapyHormone therapyHormone deprivationPharmacological blockadeTargeted therapyParacrine mechanismsTumor cellsMouse modelProstateClinical testingOrganoid culturesTherapyCancer
2017
Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance
Ku S, Rosario S, Wang Y, Mu P, Seshadri M, Goodrich Z, Goodrich M, Labbé D, Gomez E, Wang J, Long H, Xu B, Brown M, Loda M, Sawyers C, Ellis L, Goodrich D. Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. Science 2017, 355: 78-83. PMID: 28059767, PMCID: PMC5367887, DOI: 10.1126/science.aah4199.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAndrogen AntagonistsAnimalsCell Line, TumorCell LineageCell PlasticityDrug Resistance, NeoplasmEnhancer of Zeste Homolog 2 ProteinEpigenesis, GeneticHumansMaleMiceMutationNeoplasm MetastasisNeoplasms, ExperimentalNeuroendocrine TumorsProstatic NeoplasmsPTEN PhosphohydrolaseRetinoblastoma-Like Protein p107SOXB1 Transcription FactorsTumor Suppressor Protein p53ConceptsAntiandrogen therapyLineage plasticityClinical responses to antiandrogen therapyResistance to antiandrogen therapyMouse modelMetastasis of prostatic adenocarcinomaResponse to antiandrogen therapyAndrogen receptor expressionProstate cancer progressionLoss of Trp53Lineage marker expressionVariant histologyProstatic adenocarcinomaRB1 lossProstate cancerReceptor expressionPTEN mutationsAntiandrogen resistanceTherapeutic resistanceMouse tumorsGene expression profilesNeuroendocrine variantsReprogramming factorsProstateHuman tumors