Estrogens and Antiestrogens in Prostate Cancer

Despite the historical use of estrogen in the treatment of PCa little is known concerning the direct biological effects they have on the prostate, what role they may play in carcinogenesis of the gland and what mechanisms mediate the therapeutic effects of these hormones/antihormones on PCa. Therapies for advanced prostate treatment are limited and effective chemopreventive strategies for PCa are lacking. The consortium projects collectively offer a comprehensive and unique approach to address these needs. Projects are selected based on their high relevance to PCa treatment and prevention, creativities in applying the state- of-the-art technologies, experience and the willingness of the investigator to work in a synergistic manner, and short translational time-frame for bringing the end products to the clinics. Three consortium projects are focused on mechanism by which estrogens may play a role in prostatic carcinogenesis. These include studies seeking to 1) identifying genetic polymorphisms of CYP1B1 that contribute to PCa risk and race-based disparity in incidence, 2) epigenetic mechanisms for silencing ER-beta, during prostate carcinogenesis, and 3) estrogen-mediated oxidative DNA damage and its prevention by antioxidants. Results from these studies may yield new diagnostic genetic tests for PCa, identify high-risk individuals and populations, and for formulating novel preventative/intervention strategies. The other three projects are directly aimed at the treatment of advanced PCa. One is concerned with the synthesis, efficacy testing and defining mechanisms of action of a new class of estrogen-based therapeutic agents. Another is a comprehensive genetic and biological investigation of the herbal-based phytoestrogen formulation, PC-SPES, commonly used as alternative medicine by PCa patients, and the last is a clinical Phase II trial to test the efficacy of DES and Faslodex in the treatment of androgen-independent PCa.