Androgen receptor and prostate cancer stem cells: biological mechanisms and clinical implications

    1. Dean G Tang1,2,3
    1. 1Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Science Park, Park Road 1C, Smithville, Texas 78957, USA
      2Program in Molecular Carcinogenesis, University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA
      3Cancer Stem Cell Institute, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
    1. Correspondence should be addressed to D G Tang; Email: dtang{at}


    Prostate cancer (PCa) contains phenotypically and functionally distinct cells, and this cellular heterogeneity poses clinical challenges as the distinct cell types likely respond differently to various therapies. Clonal evolution, driven by genetic instability, and intraclonal cancer cell diversification, driven by cancer stem cells (CSCs), together create tumor cell heterogeneity. In this review, we first discuss PCa stem cells (PCSCs) and heterogeneity of androgen receptor (AR) expression in primary, metastatic, and treatment-failed PCa. Based on literature reports and our own studies, we hypothesize that, whereas PCSCs in primary and untreated tumors and models are mainly AR, PCSCs in CRPCs could be either AR+ or AR−/lo. We illustrate the potential mechanisms AR+ and AR PCSCs may employ to propagate PCa at the population level, mediate therapy resistance, and metastasize. As a result, targeting AR alone may not achieve long-lasting therapeutic efficacy. Elucidating the roles of AR and PCSCs should provide important clues to designing novel personalized combinatorial therapeutic protocols targeting both AR+ and AR PCa cells.

    • Revision received 13 August 2015
    • Accepted 18 August 2015
    • Made available online as an Accepted Preprint 18 August 2015
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