| Summary: | Androgen deprivation therapy (ADT), which aims to reduce androgen–androgen receptor (AR) signaling, is the normal method of prostate cancer treatment. Despite its early success in suppressing prostate tumor growth, the therapy eventually fails, leading to recurrent hormone-refractory tumor growth. Recent studies have been carried out with stromal cell-specific or fibroblast-specific AR knockout mice or prostate stromal-specific and epithelial-specific AR knockout transgenic mice prostate cancer models and in vitro and in vivo studies of various human prostate cancer cells with knock-in and knock-out of the AR. These have indicated that the AR in prostatic stroma acts as a proliferation stimulator and survival factor, whereas epithelial AR acts as a survival factor for epithelial luminal cells and stromal smooth muscle cell differentiation, and as a suppressor for epithelial basal intermediate cell proliferation. These two opposite roles of the stromal and epithelial AR pose a major challenge for ADT and should be taken into account when developing new therapies targeting AR in selective cells.
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