Beyond Enzalutamide and Abiraterone: What's Next in Androgen Therapy?

摘要

With the approvals of abiraterone and enzalutamide and the positioning of these agents in the pre-docetaxel castration resistant prostate cancer (CRPC) treatment space, men with prostate cancer and providers are now faced with the new dilemma of a rising prostate-specific antigen (PSA) and progressive disease despite the use of these potent hormonal agents. This rise in PSA in the majority of progressive patients likely reflects persistent activity of the wild-type or amplified androgen receptor (AR), AR mutants or deletion/splice variants of the ligand binding domain, or activation of other nuclear receptors that overlap with AR activity, such as the glucocorticoid receptor. Some men, however, progress radiographically or symptomatically in the absence of a substantial rise in serum PSA, indicating a shift away from hormone signaling dependence or a highly altered AR transcriptome.