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  • Title: [CYP17A1 inhibitors in prostate cancer: mechanisms of action independent of the androgenic pathway].
    Author: Audenet F, Murez T, Ripert T, Villers A, Neuzillet Y.
    Journal: Prog Urol; 2013 Oct; 23 Suppl 1():S9-15. PubMed ID: 24314739.
    Abstract:
    INTRODUCTION: The objective of this article is to review the mechanisms of action of abiraterone acetate, independently of the androgenic pathway. MATERIAL AND METHOD: A systematic review of the literature was carried out on Medline and Embase databases. RESULTS: Inhibition of CYP17A1 with abiraterone acetate induces changes in steroid metabolism, whose main component is the reduction of DHEA and androstenedione synthesis. This results in inhibition of androgen pathway in prostatic cancerous epithelial cell. Regardless of androgen activation pathway, abiraterone acetate could also act via an alternative mechanism of action not fully elucidated. Stromal cells, like tumor cells, could undergo the effects of CYP17A1 inhibition, resulting in blocking the production of secondary mediators that contribute to tumor progression. Similarly, it has been suggested that abiraterone acetate efficacy may be related to its ability to alter intratumoral concentrations of estrogen and progesterone. CONCLUSION: The validation of these mechanisms could contribute to improved therapeutic strategies based on the use of abiraterone acetate alone or in combination.
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