Next-generation sequencing of advanced prostate cancer treated with androgen-deprivation therapy

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Rajan P., Sudbery I.M., Villasevil M.E.M., Mui E., Fleming J., Davis M., Ahmad I., Edwards J., Sansom O.J., Sims D., Ponting C.P., Heger A., McMenemin R.M., Pedley I.D., Leung H.Y.

European Urology 2014 

Background Androgen-deprivation therapy (ADT) is standard treatment for locally advanced or metastatic prostate cancer (PCa). Many patients develop castration resistance (castration-resistant PCa [CRPC]) after approximately 2-3 yr, with a poor prognosis. The molecular mechanisms underlying CRPC progression are unclear. Objective To undertake quantitative tumourtranscriptome profiling prior to and following ADT to identify functionally important androgen-regulated pathways or genes that may be reactivated in CRPC. Design, setting, and participants RNA sequencing (RNA-seq) was performed on tumour-rich, targeted prostatic biopsies from seven patients with locally advanced or metastatic PCa before and approximately 22 wk after ADT initiation. Differentially regulated genes were identified in treatment pairs and further investigated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on cell lines and immunohistochemistry on a separate CRPC patient cohort. Functional assays were used to determine the effect of pathway modulation on cell phenotypes. Outcome measurements and statistical analysis We searched for gene expression changes affecting key cell signalling pathways that may be targeted as proof of principle in aCRPC in vitro cell line model…(vermás)


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