The androgen-deprivation therapy (ADT) to systematically suppress/reduce androgens binding to the androgen receptor (AR) has been a standard therapy for prostate cancer (PCa), yet most of ADT eventually fails leading to the recurrence of castration resistant PCa.
Here we found that the PCa patients who received ADT had increased PCa stem/progenitor cells population. The addition of the anti-androgen, Casodex, or AR-siRNA in various PCa cells led to increased stem/progenitor cells, while in contrast, addition of functional AR led to decreased stem/progenitor cells population, but increased non-stem/progenitor cell population, suggesting that AR functions differentially in PCa stem/progenitor vs non-stem/progenitor cells. Therefore, the current ADT might result in an undesired expansion of PCa stem/progenitor cells population, which explains why this therapy fails. Using various human PCa cell lines and 3 different mouse models, we concluded that targeting PCa non-stem/progenitor cells with AR degradation enhancer ASC-J9® and targeting PCa stem/progenitor cells with 5-AZA and γ-TT resulted in significant suppression of the PCa at the castration resistant stage. This suggests a combinational therapy that simultaneously targets both stem/progenitor and non-stem/progenitor cells will lead to better efficacy and may become a new therapy to battle the PCa before and after castration resistant stages.
Written by:
Lee SO, Ma Z, Yeh CR, Luo J, Lin TH, Lai KP, Yamashita S, Liang L, Tian J, Li L, Jiang Q, Huang CK, Niu Y, Yeh S, Chang C. Are you the author?
George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, USA.
Reference: J Mol Cell Biol. 2012 Jul 24. Epub ahead of print.
doi: 10.1093/jmcb/mjs042
PubMed Abstract
PMID: 22831834
UroToday.com Investigative Urology Section
