A Knock-in Reporter for a Novel AR-Targeted Therapy

Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in American men. Conventional treatment options for this deadly disease are based on deprivation of androgens from patients, a strategy that is often referred to as castration. While these treatments are initially effective, prostate cancer cells often resume growth and develop into aggressive tumors after an average of 24 months. Sadly, once prostate cancer becomes resistant to castration-based therapy, treatment options are very limited and often unsuccessful. This is one of the major reasons why the death rate of prostate cancer remains high. Hence, there is an imperative need to develop novel therapies for treating advanced, castration-resistant prostate cancer. The purpose of this proposal is to address this imperative need and to employ an emerging biotechnology that can precisely modify genomic DNA to develop an innovative drug screen assays that allow for quick, convenient, and cost-efficient identification of compounds that can counteract androgen receptor (AR), the major protein causing castration resistance, thereby inhibiting growth of therapy-resistant prostate cancer cells. Optimization of the structures of these AR-targeted compounds will ultimately lead to the discovery of clinically applicable drugs for treating patients with advanced, castration-resistant prostate cancer. Our proposed work is therefore relevant to the Prostate Cancer Research Program (PCRP) overarching challenges and will contribute to PCRP mission of eliminating death and suffering from prostate cancer.