June 1, 2021

SMRT Sequencing of full-length androgen receptor isoforms in prostate cancer reveals previously hidden drug resistant variants

Author(s): Clark, Tyson A. and Kohli, Manish and Ho, Yeung and Van Etten, Jamie L. and Li, Yingming and Dehm, Scott M. and Hillman, David W. and Henzler, Christine and Yang, Rendong and Silverstein, Kevin and Tseng, Elizabeth and Hon, Ting and Nolden, Laura and Wang, Liguo and Wang, Liewei

Prostate cancer is the most frequently diagnosed male cancer. For prostate cancer that has progressed to an advanced or metastatic stage, androgen deprivation therapy (ADT) is the standard of care. ADT inhibits activity of the androgen receptor (AR), a master regulator transcription factor in normal and cancerous prostate cells. The major limitation of ADT is the development of castration-resistant prostate cancer (CRPC), which is almost invariably due to transcriptional re-activation of the AR. One mechanism of AR transcriptional re-activation is expression of AR-V7, a truncated, constitutively active AR variant (AR-V) arising from alternative AR pre-mRNA splicing. Noteworthy, AR-V7 is being developed as a predictive biomarker of primary resistance to androgen receptor (AR)-targeted therapies in CRPC. Multiple additional AR-V species are expressed in clinical CRPC, but the extent to which these may be co-expressed with AR-V7 or predict resistance is not known.

Organization: PacBio
Year: 2017

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