A brief history of intracrine androgen metabolism by castration-recurrent prostate cancer.

This mini-review describes the evolution of the concept of intracrine androgen metabolism by prostate cancer during androgen deprivation therapy. Persistence of androgen receptor protein in the face of castrate circulating levels of testosterone could not be explained fully by hypersensitization or mutation of the androgen receptor. The hypothesis that castration-recurrent prostate cancer produced its own testosterone was proven using radioimmunoassay and mass spectrometry methods adopted for use in prostate tissue. Intracrine synthesis of testicular androgens led to FDA approval of abiraterone, an inhibitor of androgen metabolism. Further understanding of intracrine androgen metabolism may allow the development of more targeted agents that perform better and do not require co-administration of prednisone that may extend survival and diminish side effects from treatment of advanced prostate cancer.