2024
Mechanism-centric regulatory network identifies NME2 and MYC programs as markers of Enzalutamide resistance in CRPC
Panja S, Truica M, Yu C, Saggurthi V, Craige M, Whitehead K, Tuiche M, Al-Saadi A, Vyas R, Ganesan S, Gohel S, Coffman F, Parrott J, Quan S, Jha S, Kim I, Schaeffer E, Kothari V, Abdulkadir S, Mitrofanova A. Mechanism-centric regulatory network identifies NME2 and MYC programs as markers of Enzalutamide resistance in CRPC. Nature Communications 2024, 15: 352. PMID: 38191557, PMCID: PMC10774320, DOI: 10.1038/s41467-024-44686-5.Peer-Reviewed Original Research
2019
TCF4 induces enzalutamide resistance via neuroendocrine differentiation in prostate cancer
Lee G, Rosenfeld J, Kim W, Kwon Y, Palapattu G, Mehra R, Kim W, Kim I. TCF4 induces enzalutamide resistance via neuroendocrine differentiation in prostate cancer. PLOS ONE 2019, 14: e0213488. PMID: 31536510, PMCID: PMC6752758, DOI: 10.1371/journal.pone.0213488.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzamidesBeta CateninCell Line, TumorDisease Models, AnimalDrug Resistance, NeoplasmHumansMaleMiceMice, KnockoutNeuroendocrine CellsNitrilesPhenylthiohydantoinProstatic NeoplasmsProtein BindingProtein TransportTranscription Factor 7-Like 2 ProteinXenograft Model Antitumor AssaysConceptsCastration-resistant prostate cancerEnzalutamide resistanceTranscription factor 4Neuroendocrine differentiationProstate cancerSecond-generation androgen receptor antagonistHuman prostate cancer cell linesLNCaP human prostate cancer cell lineResistant prostate cancerProstate cancer cell linesStandard of careAndrogen receptor antagonistMouse xenograft modelExpression levelsCell linesTCF4 overexpressionCancer cell linesMedian timeClinical benefitReceptor antagonistNeuroendocrine markersMetastatic CaPTreatment resistanceXenograft modelParental cell line
2017
Intracrine androgen biosynthesis in renal cell carcinoma
Lee G, Han C, Kwon Y, Patel R, Modi P, Kwon S, Faiena I, Patel N, Singer E, Ahn H, Kim W, Kim I. Intracrine androgen biosynthesis in renal cell carcinoma. British Journal Of Cancer 2017, 116: 937-943. PMID: 28253524, PMCID: PMC5379152, DOI: 10.1038/bjc.2017.42.Peer-Reviewed Original ResearchMeSH KeywordsAbiraterone AcetateAndrogensAnimalsAntineoplastic AgentsApoptosisBenzamidesBlotting, WesternCarcinoma, Renal CellCell ProliferationDihydrotestosteroneFemaleHumansImmunoenzyme TechniquesKidney NeoplasmsMaleMiceMice, NudeNitrilesOrchiectomyPhenylthiohydantoinPrognosisProstatic NeoplasmsProstatic Neoplasms, Castration-ResistantReal-Time Polymerase Chain ReactionReceptors, AndrogenReverse Transcriptase Polymerase Chain ReactionRNA, MessengerTestosteroneTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsRenal cell carcinomaCastration-resistant prostate cancerRCC cell linesAnti-androgen therapyHuman RCC cell linesAndrogen biosynthesisAbiraterone acetateCell carcinomaAndrogen receptorTumor volumeCell linesAndrogen deprivation therapyHigher tumor stageProstate cancer patientsMouse xenograft studiesGenitourinary cancersTumor suppressionSignificant tumor suppressionRCC patientsTumor stageCancer patientsMale miceProstate cancerIntratumoral steroidogenesisXenograft studies
2014
Enzalutamide: looking back at its preclinical discovery
Ha Y, Kim I. Enzalutamide: looking back at its preclinical discovery. Expert Opinion On Drug Discovery 2014, 9: 837-845. PMID: 24820058, DOI: 10.1517/17460441.2014.918947.Peer-Reviewed Original ResearchConceptsCastration-recurrent PCaFirst-line therapyProstate cancerClinical developmentCastration-recurrent prostate cancerStandard first-line therapyAndrogen-AR axisAR agonist activityMetastatic prostate cancerAR nuclear translocationSelective AR modulatorsFurther clinical studiesAndrogen receptor antagonistPre-clinical discoveryDrug clinical developmentSequential therapyOverall survivalTargeted agentsReceptor antagonistClinical studiesPreclinical discoveryNew agentsAR modulatorsAgonist activityFDA approval
2013
Bone morphogenetic protein‐6 induces castration resistance in prostate cancer cells through tumor infiltrating macrophages
Lee G, Jung Y, Ha Y, Kim J, Kim W, Kim I. Bone morphogenetic protein‐6 induces castration resistance in prostate cancer cells through tumor infiltrating macrophages. Cancer Science 2013, 104: 1027-1032. PMID: 23710822, PMCID: PMC7657257, DOI: 10.1111/cas.12206.Peer-Reviewed Original ResearchMeSH KeywordsAndrogen Receptor AntagonistsAndrogensAnilidesAnimalsBenzamidesBenzofuransBone Morphogenetic Protein 6Cell Line, TumorDihydrotestosteroneHumansInterleukin-6Lymphocytes, Tumor-InfiltratingMacrophagesMaleMiceNitrilesPhenylthiohydantoinPromoter Regions, GeneticProstatic Neoplasms, Castration-ResistantQuinolinesReceptors, AndrogenTosyl CompoundsUp-RegulationConceptsCaP cell linesCastration resistanceInterleukin-6Castration-resistant prostate cancerContext of macrophagesHuman CaP cell linesExpression of ARRemoval of macrophagesAndrogen receptor mRNAProstate cancer progressionBMP-6Presence of dihydrotestosteroneProstate cancer cellsCell linesPresence of macrophagesPleiotropic growth factorBone morphogenetic proteinClodronate liposomesTRAMP-C1AR upregulationProstate cancerAndrogen hypersensitivityMacrophage coculturesReceptor mRNACell countEnzalutamide for the treatment of castration-resistant prostate cancer.
Ha Y, Goodin S, DiPaola R, Kim I. Enzalutamide for the treatment of castration-resistant prostate cancer. Drugs Of Today 2013, 49: 7-13. PMID: 23362491, DOI: 10.1358/dot.2013.49.1.1910724.Peer-Reviewed Original ResearchConceptsCastration-resistant prostate cancerPhase III trialsAndrogen receptorIII trialsProstate cancerTreatment of CRPCMetastatic castration-resistant prostate cancerPhase I/II studyEffectiveness of enzalutamidePrior docetaxel chemotherapyBinding of AROptimal safety profileMajor clinical challengeSignificant antitumor activityPrior chemotherapyDocetaxel chemotherapyII studySafety profileClinical challengePreclinical studiesDrug AdministrationTumor growthChemotherapyU.S. FoodAntitumor activity