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Status |
Public on Jan 11, 2022 |
Title |
Modeling androgen deprivation therapy-induced prostate cancer dormancy and its clinical implications |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Purpose: Treatment-induced tumor dormancy is a state in cancer progression where residual disease is present but remains asymptomatic. Dormant cancer cells are treatment-resistant and responsible for cancer recurrence and metastasis. Prostate cancer (PCa) treated with androgen-deprivation therapy (ADT) often enters a dormant state. ADT-induced PCa dormancy remains poorly understood due to the challenge in acquiring clinical dormant PCa cells and the lack of representative models. We, therefore, aimed to develop clinically relevant models that can be used for studying ADT-induced PCa dormancy. Experimental design: Dormant PCa models were established by castrating mice bearing PCa patient-derived xenografts (PDXs) of hormonal naïve or sensitive PCa. Dormancy status and tumor relapse were monitored and evaluated. Paired pre- and post-castration (dormant) PDX tissues were subjected to morphological and transcriptome profiling analyses. Results: We established eleven ADT-induced dormant PCa models that closely mimicked the clinical courses of ADT-treated PCa. We identified two ADT-induced dormancy subtypes that differed in morphology, gene expression, and relapse rates. We discovered transcriptomic differences in pre-castration PDXs that predisposed the dormancy response to ADT. We further developed a dormancy subtype-based, predisposed gene signature that was significantly associated with ADT response in hormonal naïve PCa and clinical outcome in castration-resistant PCa treated with ADT or androgen-receptor pathway inhibitors.
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Overall design |
Mice bearing patient-derived prostate cancer xenografts were surgically castrated. Tissues for microarray profiling and analyses were harvested at pre-castration and post-castration 12 week timepoints, respectively.
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Contributor(s) |
Dong X, Xue H, Mo F, Lin Y, Lin D, Wong NK, Sun Y, Wilkinson S, Ku AT, Hao J, Ci X, Wu R, Haegert A, Silver R, Taplin M, Balk S, Alumkal JJ, Sowalsky AG, Gleave M, Collins C, Wang Y |
Citation(s) |
35082166 |
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Submission date |
Jan 11, 2022 |
Last update date |
Apr 13, 2022 |
Contact name |
Yuzhuo Wang |
Organization name |
University of British Columbia
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Department |
Vancouver Prostate Centre
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Lab |
The Living Tumor Laboratory
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Street address |
2660 Oak Street
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City |
Vancouver |
State/province |
BC |
ZIP/Postal code |
V6H 3Z6 |
Country |
Canada |
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Platforms (1) |
GPL14550 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version) |
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Samples (22)
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Relations |
BioProject |
PRJNA796371 |
Supplementary file |
Size |
Download |
File type/resource |
GSE193500_RAW.tar |
68.2 Mb |
(http)(custom) |
TAR (of TXT) |
Processed data included within Sample table |
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