Novel Approaches & New Therapeutic Platforms
J. Kellogg Parsons (MCC)
Rana McKay (MCC)
Catriona Jamieson (MCC)
Metastatic castration resistant prostate cancer (CRPC) is a lethal disease that claims 30,000 lives annually in the U.S. Although current approved drugs will slow the growth of metastatic CRPC, development of drug resistance—and cancer progression—is inevitable. It is therefore imperative to develop new treatments to improve survival. As we learn more about the factors driving progression of metastatic prostate cancer, we have discovered that the Wnt signaling pathway is activated in these patients.The Wnt pathway possibly confers resistance to standard drug treatments, including hormone therapy and chemotherapy. Prior attempts to target this pathway have been unsuccessful. Cirmtuzumab, a ROR1-binding monoclonal antibody which inhibits the Wnt pathway, is a compelling new drug with the potential to treat CRPC by blocking Wnt activity. Cirmtuzumab was developed at UCSD by Drs. Kipps, Jamieson, and Carson. Studies are underway in chronic lymphocytic leukemia and breast cancer. We hypothesize that the addition of cirmtuzumab to docetaxel, a chemotherapy drug, will be safe and effective for patients with metastatic CRPC.To test this hypothesis for the first time, we propose a clinical trial of cirmtuzumab combined with docetaxel in men with prostate cancer. To better understand mechanisms of drug resistance, and which patients might benefit most from cirmtuzumab, we will perform molecular analyses of cancer tissue and blood samples throughout the study. This multidisciplinary, collaborative effort harnesses the expertise of clinical and laboratory scientists at UCSD; and if successful, may reveal a new and unique drug to improve survival for patients with CRPC.