Abstract
While several hypotheses have been put forward to explain how prostate tumors become resistant to androgen deprivation therapy, the mechanism by which prostate tumors have increased androgen concentrations as compared to the serum has been poorly explored. Using a stromal/epithelial cell co-culture model, Mizokami et al. have demonstrated how prostate-, bone- and prostate tumor-derived stromal cells participate with tumor-derived epithelial cells (i.e., LNCaP cells) to produce active androgens from a readily available substrate during androgen deprivation therapy, dehydroepiandrosterone (DHEA). Although these experiments are conducted in vitro, they provide a basis for the possibility of intratumoral DHEA-mediated androgen synthesis mechanisms that may underlie androgen receptor reactivation during androgen deprivation in many prostate tumors. Moreover, Mizokami et al. have shown that dutasteride, previously considered an SRD5A inhibitor, also inhibits the interplay between stromal and epithelial cells in the synthesis of testosterone. Herein, we summarize this study and comment on therapeutic implications.