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 ResearchAndrogen Receptor AntagonistsBenzamidesHumansMaleNM23 Nucleoside Diphosphate KinasesProstatic Neoplasms, Castration-ResistantSignal Transduction
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
2015
Pharmacokinetics, pharmacodynamics and clinical efficacy of abiraterone acetate for treating metastatic castration-resistant prostate cancer
Han C, Patel R, Kim I. Pharmacokinetics, pharmacodynamics and clinical efficacy of abiraterone acetate for treating metastatic castration-resistant prostate cancer. Expert Opinion On Drug Metabolism & Toxicology 2015, 11: 967-975. PMID: 25936418, DOI: 10.1517/17425255.2015.1041918.Peer-Reviewed Original ResearchMeSH KeywordsAbiraterone AcetateAndrogensAntineoplastic AgentsDisease ProgressionDrug Resistance, NeoplasmHumansMaleMolecular Targeted TherapyNeoplasm MetastasisPatient SelectionProstatic Neoplasms, Castration-ResistantSurvival RateConceptsCastration-resistant prostate cancerMetastatic castration-resistant prostate cancerAbiraterone acetateMetastatic CRPCProstate cancerPhase III trialsBetter patient selectionHigh-level evidenceRisk of hypertensionDrug resistance patternsCurrent clinical challengesIntratumoral androgensOverall tolerabilityIII trialsPatient selectionClinical efficacySafety profileDevelopment of resistanceTreatment modalitiesDisease progressionTargeted therapyAndrogen sourceClinical challengeAndrogen signalingCYP 17
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 ResearchMeSH KeywordsAndrogen Receptor AntagonistsAnimalsAntineoplastic AgentsBenzamidesDrug Evaluation, PreclinicalHumansMaleNitrilesPhenylthiohydantoinProstatic Neoplasms, Castration-ResistantConceptsCastration-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 approvalProstate cancer bone metastases acquire resistance to androgen deprivation via WNT5A-mediated BMP-6 induction
Lee G, Kang D, Ha Y, Jung Y, Chung J, Min K, Kim T, Moon K, Chung J, Lee D, Kim W, Kim I. Prostate cancer bone metastases acquire resistance to androgen deprivation via WNT5A-mediated BMP-6 induction. British Journal Of Cancer 2014, 110: 1634-1644. PMID: 24518599, PMCID: PMC3960605, DOI: 10.1038/bjc.2014.23.Peer-Reviewed Original ResearchMeSH KeywordsAdultAndrogen AntagonistsAnilidesBone Morphogenetic Protein 6Bone NeoplasmsCell CommunicationCell Growth ProcessesCell Line, TumorHumansMaleMiddle AgedNeoplasm MetastasisNitrilesOrchiectomyProstatic Neoplasms, Castration-ResistantProto-Oncogene ProteinsReceptors, AndrogenRetrospective StudiesStromal CellsTosyl CompoundsWnt ProteinsWnt-5a ProteinConceptsCastration-resistant prostate cancerBone stromal cellsBone metastasesBone morphogenetic protein 6Castration resistanceCaP cell linesStromal cellsProstate cancerPrimary androgen deprivation therapyProstate-specific antigen progressionProstate cancer bone metastasisAndrogen-deprived mediumBone-tumor interactionAndrogen deprivation therapyFirst-line therapyCancer bone metastasisMetastatic prostate cancerAbsence of androgenAndrogen-depleted conditionsNF-κB pathwayCell linesPolymerase chain reaction arrayBMP-6 expressionAdvanced CaPDeprivation therapy
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 count
2011
Macrophages induce neuroendocrine differentiation of prostate cancer cells via BMP6‐IL6 Loop
Lee G, Kwon S, Lee J, Jeon S, Jang K, Choi H, Lee H, Kim W, Lee D, Kim I. Macrophages induce neuroendocrine differentiation of prostate cancer cells via BMP6‐IL6 Loop. The Prostate 2011, 71: 1525-1537. PMID: 21374653, DOI: 10.1002/pros.21369.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Morphogenetic Protein 6Cell DifferentiationCell Line, TumorCoculture TechniquesHumansInterleukin-6MacrophagesMaleMice, KnockoutMonocytesNeuroendocrine CellsProstatic Neoplasms, Castration-ResistantReceptors, AndrogenConceptsProstate cancer cellsHormone-refractory prostate cancerRefractory prostate cancerNeuroendocrine differentiationBone morphogenetic protein 6IL-6Cancer cellsProstate cancerInterleukin-6 knockout miceTRAMP-C2 cell lineHuman prostate cancer tissuesNeuroendocrine cellsCell linesParathyroid hormone-related peptideTRAMP-C2 prostate cancer cellsTRAMP-C2 cellsMacrophage-depleted miceProstate Cancer Neuroendocrine DifferentiationIL-6 expressionTHP-1 human monocytic cell lineHormone-related peptideProstate cancer tissuesHuman monocytic cell lineRAW 264.7 murine macrophage cell lineEffect of macrophages