Role of targeted therapy in the treatment of advanced prostate cancer.

Overview

Over the past decade, the treatment of advanced prostate cancer has developed significantly, and perhaps the most dramatic shift came in 2004 with the demonstration that docetaxel-based chemotherapy significantly improved overall survival in patients with castration-resistant prostate cancer. This led to a significant expansion of the role of chemotherapy in the management of prostate cancer. In addition, there is now considerable progress being made in the development of more effective antiandrogens, cytochrome P17 inhibitors, novel chemotherapy regimens, targeted therapies, and immunotherapies that can complement existing therapies and may soon become integrated into the treatment paradigm. Progress in our understanding of molecular signalling pathways that play an important role in prostate cancer has stimulated the investigation of targeted therapies, including antiangiogenic agents, bone-targeted agents, and specific inhibitors of key signalling molecules and chaperone proteins. For the most part, targeted agents are being combined with chemotherapy, similar to the approach taken in other solid tumours. Various therapeutic vaccine strategies also appear to have potential in the treatment of advanced prostate cancer. However, the development of new approaches to the treatment of prostate cancer presents many challenges that will demand collaboration and consensus building with respect to biomarkers for patient selection, clinical endpoints, and trial designs.