Treatment of metastatic prostate cancer. Lessons from the androgen receptor.

The exquisite hormonal dependence of prostate cancer continues to provide an opportunity and a challenge for oncologists. It is clear that future efforts in the laboratory should include determining the frequency and spectrum of AR mutations in AI prostate cancer, the development of more effective antiandrogens, and understanding in greater detail how the AR stimulates the growth of prostate cancers. These efforts may eventually lead to treatments that greatly reduce any stimulatory effects of the AR on prostate cells, possibly resulting in a significant improvement in disease-free survival and, perhaps in conjunction with other modalities, cure of some earlier stages of disease. And even for patients with advanced disease, because hormonal therapy is generally fairly well tolerated even in the typically older prostate cancer patient, defining the contribution of AR-mediated growth to AI disease will be critically important.