关键词：医药；治疗技术；前列腺癌；临床试验；基因；抑制剂
摘 要：The goal of this research is to firmly establish the mechanism of androgen receptor (AR)-JunD heterodimer induction of the SSAT gene leading to oxidative stress that contributes to the development and progression of prostate cancer (PCa), and to identify small molecules that specifically inhibit this AR-JunD interaction and prevent development/progression of PCa in pre-clinical models. Data from this research will identify the most efficacious drug to be further developed in preclinical toxicity testing and clinical trials for PCa that fall beyond the scope of this proposal. Significant findings during Year 2 of the research include: identification of two non- antiandrogenic AR-JunD inhibitors that significantly inhibit ROS production and androgen-dependent and -independent growth in PCa cells; and determination that the lead compound is orally bioavailable and therefore a promising clinical drug candidate to be further tested for efficacy against preclinical animal models of PCa as proposed.