Identification of Master Regulators of Advanced and Castrate-Resistant Prostate Cancer Under Treatment with Abiraterone

Prostate cancer screening is widely performed, especially in the United States and Europe, and prostate cancer is therefore, in the vast majority of patients, detected at early stages and curable. However, curative treatment options at advanced disease stages are limited, and ultimately all patients with advanced or widespread disease will die of their disease.

Most recently the Food and Drug Administration (FDA) has approved a new drug, Abiraterone, in patients who have advanced disease or disease spread to soft tissue or bone despite treatment with chemotherapy. However, despite a significant survival advantage under treatment with this drug, previous studies have shown that invariably most of the patients on Abiraterone will become resistant to this drug and will therefore develop progressive lethal disease. The resistance mechanisms that prostate cancer cells develop ultimately to Abiraterone are not clearly understood.

In this proposal we use a human prostate cancer cells in to study the growth of tumors, and their response rate to Abiraterone, but most importantly, we are aiming at characterizing cellular and molecular changes, pathways, and key genes within the prostate cancer cells that help them to escape treatment and that lead to their development of resistance.

Our comprehensive approach will help understand differences in response rates, as well as identify genetic differences between prostate cancer cells that respond to Abiraterone versus those that do not respond, and will help identify genetic differences before, during, and after treatment with Abiraterone. Consequently, we will further our understanding of resistance mechanisms under treatment with this drug and identify new targets for new and more effective drugs for the treatment of advanced prostate cancer.

Career Goals: After graduation from residency in June 2013, I will become Assistant Professor of Urology at Columbia University Medical Center with a clinical focus on prostate cancer. During my Fellowship and Residency, I continuously conducted research, published several manuscripts, and presented at international urologic conferences. My goal is to continue to perform research on prostate cancer in order to advance knowledge on the treatment of advanced disease. This research proposal will enable me to acquire the skills and knowledge to become a productive, independent prostate cancer researcher to better understand tumor biology and to develop new, alternative therapies and drugs for patients with advanced disease, resistant to today's available treatment options. Especially the analysis of effects of currently available drugs for the treatment of prostate cancer in men, incorporated in mice as described in this proposal, will allow me as a clinical urologist to complement and integrate my clinical knowledge into the conducted research as a foundation for future basic research.