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cells, fig, crpc, supplementary, lncap, pubmed, cancer, lapc, arko, cell, enza, tumors, pca, arlo, tumor, article, prostate, google, scholar, bcl, cas, genes, expression, clones, mice, data, gene, analysis, central, androgen, therapeutic, arhi, castrated, signaling, patient, experiments, stem, castration, abt, treatment, human, growth, upregulated, models, rnaseq, receptor, xenograft, levels, resistance, results,

Topics {✒️}

nature portfolio long-acting d-trp-6-lhrh microcapsules research center privacy policy genome editing-derived ar+ complimentary genome-editing techniques employ genome-editing technologies advertising hedgehog-dependent tumor-initiating cells nature 510 nature androgen-independent lncap-ai cells52 androgen receptor-axis imaging east hospital es/tools/venny/ androgen-independent prostate cancer high-throughput sequencing data synthesize cdna libraries reprints recognize full-length ar �androgen-independent/ai’ patient tumors ar/foxa1 signaling axis rna-seq data set trop2+cd45− cell population inter-dependent symbiotic relationship ar−/lo crpc cells/clones higher tumor-regenerating activities enza-insensitive ar-/lo crpc single cell-derived clones c-terminal truncated variants org/gsea/doc/gsea userguideframe enza-resistant de novo ar-/lo cell population ar-ko cells possess full size image immune/inflammation gene signatures castration-resistant prostate cancer proteins including c-myc30 ar−/lo crpc possess called ar-ko clones ar−/lo metastatic clones2 rajan data set22 ar+ cell-derived tumors ar + lncap cells based combinatorial anti-csc strategies require androgen/ar signaling ar−/lo pca cells single ar-ko cells ar-ko pca cells ar-deficient pca cells

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         headline:Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses
         description:Expression of androgen receptor (AR) in prostate cancer (PCa) is heterogeneous but the functional significance of AR heterogeneity remains unclear. Screening ~200 castration-resistant PCa (CRPC) cores and whole-mount sections (from 89 patients) reveals 3 AR expression patterns: nuclear (nuc-AR), mixed nuclear/cytoplasmic (nuc/cyto-AR), and low/no expression (AR−/lo). Xenograft modeling demonstrates that AR+ CRPC is enzalutamide-sensitive but AR−/lo CRPC is resistant. Genome editing-derived AR+ and AR-knockout LNCaP cell clones exhibit distinct biological and tumorigenic properties and contrasting responses to enzalutamide. RNA-Seq and biochemical analyses, coupled with experimental combinatorial therapy, identify BCL-2 as a critical therapeutic target and provide proof-of-concept therapeutic regimens for both AR+/hi and AR−/lo CRPC. Our study links AR expression heterogeneity to distinct castration/enzalutamide responses and has important implications in understanding the cellular basis of prostate tumor responses to AR-targeting therapies and in facilitating development of novel therapeutics to target AR−/lo PCa cells/clones. The functional significance of the observed heterogeneity of androgen receptor (AR) expression in prostate cancer is unknown. Here the authors show AR expression heterogeneity is associated with distinct castration/enzalutamide responses and identify BCL-2 as a potential therapeutic target in castration-resistant prostate cancer.
         datePublished:2018-09-06T00:00:00Z
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            Prostate cancer
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ScholarlyArticle:
      headline:Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses
      description:Expression of androgen receptor (AR) in prostate cancer (PCa) is heterogeneous but the functional significance of AR heterogeneity remains unclear. Screening ~200 castration-resistant PCa (CRPC) cores and whole-mount sections (from 89 patients) reveals 3 AR expression patterns: nuclear (nuc-AR), mixed nuclear/cytoplasmic (nuc/cyto-AR), and low/no expression (AR−/lo). Xenograft modeling demonstrates that AR+ CRPC is enzalutamide-sensitive but AR−/lo CRPC is resistant. Genome editing-derived AR+ and AR-knockout LNCaP cell clones exhibit distinct biological and tumorigenic properties and contrasting responses to enzalutamide. RNA-Seq and biochemical analyses, coupled with experimental combinatorial therapy, identify BCL-2 as a critical therapeutic target and provide proof-of-concept therapeutic regimens for both AR+/hi and AR−/lo CRPC. Our study links AR expression heterogeneity to distinct castration/enzalutamide responses and has important implications in understanding the cellular basis of prostate tumor responses to AR-targeting therapies and in facilitating development of novel therapeutics to target AR−/lo PCa cells/clones. The functional significance of the observed heterogeneity of androgen receptor (AR) expression in prostate cancer is unknown. Here the authors show AR expression heterogeneity is associated with distinct castration/enzalutamide responses and identify BCL-2 as a potential therapeutic target in castration-resistant prostate cancer.
      datePublished:2018-09-06T00:00:00Z
      dateModified:2018-09-06T00:00:00Z
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      pageEnd:17
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      keywords:
         Cancer stem cells
         Prostate cancer
         Tumour heterogeneity
         Urological cancer
         Science
         Humanities and Social Sciences
         multidisciplinary
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      name:Program in Molecular Carcinogenesis, University of Texas Graduate School for Biomedical Sciences (GSBS), Houston, USA
      name:Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, USA
      name:Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, USA
      name:Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, USA
      name:Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, USA
      name:Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, USA
      name:Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, USA
      name:Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, USA
      name:Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, USA
      name:Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, USA
      name:Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, USA
      name:Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, USA
      name:Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, USA
      name:Department of Pathology, Duke University of School of Medicine, Durham, USA
      name:Caryl and Israel Englander Institute for Precision Medicine, New York-Presbyterian Hospital, Weill Cornell Medical College, New York, USA
      name:Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, USA
      name:Caryl and Israel Englander Institute for Precision Medicine, New York-Presbyterian Hospital, Weill Cornell Medical College, New York, USA
      name:Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, New York, USA
      name:Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, USA
      name:Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, USA
      name:Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, USA
      name:Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, USA
      name:Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, USA
      name:Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, USA
      name:Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, USA
      name:Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, USA
      name:Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, USA
      name:Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, USA
      name:Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, USA
      name:Cancer Stem Cell Institute, Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China

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