Pre-Clinical Development of New Autophagy Targeting Drugs for Bone Metastatic Prostate Cancer

Novel Approaches and New Therapeutics

Nicholas Cosford (SBP)

Christina Jamieson (UCSD)

One in six men will be diagnosed with prostate cancer (PCa), making it one of the leading health problems affecting men in today’s society. Patients diagnosed during the earlier stages are surviving longer due to improved therapies and the prevalence of prostate-specific antigen (PSA) testing. A growing number of these patients, however, go on to develop advanced PCa. The main treatment for advanced prostate cancer (PCa) is androgen pathway directed therapy (APDT). Unfortunately, patients invariably become resistant to APDT, and their cancer metastasizes - most often to bone - for which there is no cure. Autophagy (ATG) plays a role as a survival pathway that contributes to cancer growth, resistance, and cell dormancy. Therefore, inhibiting ATG is a novel mechanism to reduce survival of PCa resistant to APDT. While cellular models of bone metastatic PCa have been difficult to generate, we have recently established patient derived cellular 2D and 3D models allowing us to evaluate treatments for this fatal disease. In our proposal we will examine a class of specific ATG inhibitors in patient bone metastatic PCa cells and evaluate their ability to reduce PCa tumor burden in mouse models alone and in combination with ADPT. These studies will allow the development of a new drug therapy for the treatment of this deadly cancer and enhance patient outcomes.