Transcriptome analysis of VCaP xenografts resistant to dual therapy with abiraterone and enzalutamide
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PROVIDER: PRJNA431777 | ENA |
REPOSITORIES: ENA
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Project description:We report RNA sequencing data on serial biopsies of prostate cancer VCaP xenografts as the tumors pass from androgen-sensitivity (Pre-Cx), to castration resistance (CRPC, castration resistant prostate cancer), onto resistance to dual therapy with abiraterone plus enzalutamide (AER). From comparison of these RNAseq data sets, we were able to determine differentially expressed genes between the AER/CRPC and Pre-Cx states that could mediate resistance to androgen deprivation therapies.
2018-12-26 | GSE109708 | GEO
Project description:Transriptome analysis of VCAP and CWR22-Pc cell lines after concomittant treatment with androgen with bicalutamide and enzalutamide
2015-10-01 | GSE62473 | GEO
Project description:The treatment of advanced prostate cancer has been transformed by novel antiandrogen therapies such as enzalutamide. We identified glucocorticoid receptor (GR) activity as modulator of enzalutamite sensitivity in the VCaP prostate cancer cell line. The GR agonist dexamethasone was sufficient to confer enzalutamide resistance whereas a GR antagonist restored sensitivity. These expression profiling data demonstrate that GR transcriptional activity overlaps with that of AR in the VCAP model. VCAP cells growing in complete media were treated with the indicated drugs in biological triplicates for 24 hours prior to harvest.
2013-12-27 | E-GEOD-51872 | biostudies-arrayexpress
Project description:The treatment of advanced prostate cancer has been transformed by novel antiandrogen therapies such as enzalutamide. We identified glucocorticoid receptor (GR) activity as modulator of enzalutamite sensitivity in the VCaP prostate cancer cell line. The GR agonist dexamethasone was sufficient to confer enzalutamide resistance whereas a GR antagonist restored sensitivity. These expression profiling data demonstrate that GR transcriptional activity overlaps with that of AR in the VCAP model.
2013-12-27 | GSE51872 | GEO
Project description:VCaP prostate cancer xenografts grown in castrated mice were treated with antiandrogen (enzalutamide), and samples were obtained during treatment response (Enza I: 5 days after initiation of the treatment) and after the treatment resistance had occurred (Enza II: 47 days after initiation of the treatment).
2022-05-02 | GSE147541 | GEO
Project description:Illumina gene array analyses of prostate cancer cell lines that had acquired resistance to Enzalutamide (MDV3100). mRNA analyses of four cell lines (CWR-R1, LAPC-4, LNCaP, and VCAP) cells that were either untreated, treated for 48hrs with Enz (short-term), or continuously grown in Enzalutamide for >6 months.
2016-02-24 | E-GEOD-78201 | biostudies-arrayexpress
Project description:Molecular mechanisms underlying resistance to androgen deprivation therapy (ADT) and, in particular, to antiandrogen Enzalutamide, in treating castration-resistant prostate cancer (CRPC), remain incompletely understood. Through screening >120 CRPC patient samples, we observed 3 expression patterns of androgen receptor (AR) protein: primarily nuclear (nuc-AR), mixed nuclear/cytoplasmic expression (nuc/cyto-AR), and low/no expression (AR-/lo). Xenograft CRPC modeling in 4 models (i.e., LNCaP, VCaP, LAPC4, and LAPC9) recapitulated the 3 AR expression patterns in castration-resistant tumors developed from parental androgen-dependent tumors. Strikingly, although the 3 CRPC models that retained AR expression (LNCaP, VCaP, and LAPC4) responded, to different levels and in different kinetics, to Enzalutamide, the AR-/lo LAPC9 CRPC was completely refractory to Enzalutamide. By combining whole-genome RNA-Seq and biochemical analyses together with experimental combinatorial therapy in the LNCaP and LAPC9 models, we identified BCL-2 as a critical therapeutic target in both AR+/hi and AR-/lo, Enzalutamide-resistant CRPC models.
2018-08-01 | GSE88752 | GEO
Project description:Background. Androgen receptor splice variant-7 (AR-V7) is a truncated form of the androgen receptor protein which lacks the ligand-binding domain, the target of enzalutamide and abiraterone, but remains constitutively active as a transcription factor. We hypothesized that detection of AR-V7 in circulating tumor cells (CTCs) from men with advanced prostate cancer would be associated with resistance to enzalutamide and abiraterone. Methods. We used quantitative reverse-transcription polymerase-chain-reaction (qRT-PCR) to interrogate CTCs for the presence or absence of AR-V7 from prospectively enrolled patients with metastatic castration-resistant prostate cancer initiating treatment with either enzalutamide or abiraterone. We examined associations between AR-V7 status and PSA response rates, PSA-progression-free-survival (PSA-PFS), clinical/radiographic-progression-free-survival (PFS), and overall survival (OS). Multivariable Cox regression analyses were performed to determine the independent effect of AR-V7 status on clinical outcomes. Results. Thirty-one enzalutamide-treated patients and thirty-one abiraterone-treated patients were enrolled, of which 38.7% and 19.4% had detectable AR-V7 from CTCs, respectively. Among men receiving enzalutamide, AR-V7–positive patients had inferior PSA response rates (0% vs 52.6%, P=0.004), PSA-PFS (median: 1.4 vs 6.0 months, P<0.001), PFS (median: 2.1 vs 6.1 months, P<0.001), and OS (median: 5.5 months vs not reached, P=0.002) compared to AR-V7–negative patients. Similarly, among men receiving abiraterone, AR-V7–positive patients had inferior PSA response rates (0% vs 68.0%, P=0.004), PSA-PFS (median: 1.3 months vs not reached, P<0.001), PFS (median: 2.3 months vs not reached, P<0.001), and OS (median: 10.6 months vs not reached, P=0.006). The negative prognostic impact of AR-V7 was maintained after adjusting for full-length-AR expression. Conclusions. Detection of AR-V7 in CTCs from patients with castration-resistant prostate cancer is associated with resistance to enzalutamide and abiraterone. A total of four metastatic castration-resistant prostate tumor samples from four patients were subjected to RNA-seq. Two samples were positive for androgen receptor splice variant 7 and the other two were negative for this variant.
2014-09-03 | E-GEOD-56701 | biostudies-arrayexpress
Project description:To identify the molecular signature associated with abiraterone acetate (AA) response and mechanisms underlying AA resistance in castration-resistant prostate cancer patient-derived xenografts (PDXs).
2016-12-22 | GSE85672 | GEO
Project description:Purpose: Monoamine oxidase A (MAOA) is a mitochondrial enzyme that degrades neurotransmitters including serotonin and norepinephrine. Its inhibitors are commonly used to treat neurologic conditions including depression. Recently, we and others identified high expression of MAOA in normal basal prostate epithelium and in high grade primary prostate cancer (PCa). Inhibition of MAOA with an irreversible inhibitor, clorgyline, induced differentiation in primary cultures of epithelial cells from normal tissues and high grade cancers. Furthermore, clorgyline treatment inhibited several oncogenic pathways in PCa cells, suggesting a clinical value of MAOA inhibitors as a pro-differentiation and anti-oncogenic therapy for high risk PCa. Here, we extended our studies to a model of advanced PCa, VCaP cells, which were derived from castration-resistant metastatic PCa and express a high level of MAOA. Methods: The growth of VCaP cells in the presence or absence of clorgyline was evaluated in vitro and in vivo. Gene expression changes in response to clorgyline were determined by microarray and validated by quantitative real-time PCR. Results: Treatment with clorgyline in vitro inhibited growth and altered the transcriptional pattern of VCaP cells in a manner consistent with the pro-differentiation and anti-oncogenic effects seen in treated primary PCa cells. Src, beta-catenin, and MAPK oncogenic pathways, implicated in androgen-independent growth and metastasis, were significantly downregulated. Clorgyline treatment of mice bearing VCaP xenografts slowed tumor growth and induced transcriptome changes similar to those noted in vitro. Conclusions: Our results support the possibility that anti-depressant drugs that target MAOA might find a new application in treating PCa. Compound Based Treatment: Clorgyline treament of VCaP cells
2010-10-25 | GSE19822 | GEO