Androgen synthesis in prostate cancer: Do all roads lead to Rome?

Abstract

The accumulation of high concentrations of signalling androgens within prostate tumours that progress despite use of androgen-deprivation therapy is a clinically important mechanism of the development of castration-resistant prostate cancer. In the past 5 years, data from a number of studies have increased our understanding of the enzymes and substrates involved in intratumoural androgen biosynthesis, and have implicated three competing pathways, which are likely to account for these observations. These pathways ('canonical', 'backdoor' and '5α-dione'), which can all ultimately generate the potent signalling androgen, dihydrotestosterone, involve many of the same enzymes, but differ in terms..