Beefing up prostate cancer therapy with performance-enhancing (anti-) steroids

Abstract

In the May 26th issue of the New England Journal of Medicine, de Bono et al. report that the inhibition of androgen synthesis by abiraterone acetate prolonged the survival of men with prostate cancer previously treated by androgen suppression.

Figure 1. Androgen-Dependent versus Androgen-Independent Prostate Cancer

The CYP17A inhibitor, abiraterone, can improve outcomes in castration-resistant prostate cancer by further reducing castration levels of androgens. This provides evidence that castration-resistant prostate cancer can often still be androgen-dependent. However, ultimately, prostate cancer cells can emerge that are resistant to abiraterone. Such cells are likely to have a truly androgen-independent phenotype, in which resistant prostate cancer cells could continue to express growth and survival pathways through AR-dependent (e.g., via mutation of AR to allow other ligands to stimulate signaling, via production of constitutively active AR isoforms lacking the ligand binding domain, or via subversion of other growth factor receptor pathways for activating AR signaling), or AR-independent mechanisms. T, testosterone; DHT, dihydrotestosterone.