Key Targets of Hormonal Treatment of Prostate Cancer: The Androgen Receptor and 5α-Reductase

The review from 2009 focused on the role of 5α-reductase (5AR) inhibition in the treatment of prostate cancer, highlighting the changes in expression of the two 5AR isoenzymes, 5AR1 and 5AR2, during the progression of the disease. It was found that 5AR1 expression increases with the aggressiveness of the cancer, while 5AR2 expression decreases from benign to malignant stages. The review suggested that monotherapy with the 5AR2 inhibitor finasteride, either alone or combined with an androgen receptor antagonist, had limited efficacy on advanced prostate cancer outcomes. However, combining an androgen receptor antagonist with a 5AR inhibitor could be a beneficial first hormonal approach for asymptomatic, locally advanced, or recurrent prostate cancer, as it maintains plasma testosterone levels and could improve quality of life and sexual function. The dual 5AR inhibitor dutasteride was noted to be generally well tolerated and capable of producing a biochemical response in some men who progressed under androgen-deprivation therapy. The conclusion was that more potent suppression of intracellular dihydrotestosterone (DHT) synthesis through 5AR inhibition could provide clinical benefits, potentially halting or delaying disease progression and possibly causing regression in advanced cases.