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The changing therapeutic landscape of castration-resistant prostate cancer

Nature Reviews Clinical Oncology volume 8, pages 597–610 (2011)Cite this article

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Abstract

Castration-resistant prostate cancer (CRPC) has a poor prognosis and remains a significant therapeutic challenge. Before 2010, only docetaxel-based chemotherapy improved survival in patients with CRPC compared with mitoxantrone. Our improved understanding of the underlying biology of CRPC has heralded a new era in molecular anticancer drug development, with a myriad of novel anticancer drugs for CRPC entering the clinic. These include the novel taxane cabazitaxel, the vaccine sipuleucel-T, the CYP17 inhibitor abiraterone, the novel androgen-receptor antagonist MDV-3100 and the radioisotope alpharadin. With these developments, the management of patients with CRPC is changing. In this Review, we discuss these promising therapies along with other novel agents that are demonstrating early signs of activity in CRPC. We propose a treatment pathway for patients with CRPC and consider strategies to optimize the use of these agents, including the incorporation of predictive and intermediate end point biomarkers, such as circulating tumor cells.

Key Points

  • Castration-resistant prostate cancer (CRPC) is associated with a poor prognosis and remains a significant therapeutic challenge

  • Before 2010, there was an urgent unmet clinical need for more-effective and well-tolerated therapies for CRPC

  • Improved understanding of the underlying biology of CRPC heralded a new era in molecular anticancer drug development

  • New treatments for CRPC imparting an overall survival benefit include cabazitaxel, sipuleucel-T, abiraterone and alpharadin

  • The management of patients with CRPC is changing; therefore, we propose a novel treatment pathway including the incorporation of predictive and intermediate end point biomarkers

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Figure 1: Key signaling cascades involved in prostate cancer.
Figure 2: Treatment paradigm for CRPC in 2011 and beyond.

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Authors and Affiliations

  1. Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Downs Road, Sutton, SM2 5PT, Surrey, UK

    Timothy A. Yap, Andrea Zivi, Aurelius Omlin & Johann S. de Bono

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All authors contributed to the research, discussion of content, writing, editing and reviewing of this manuscript.

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T. A. Yap, A. Zivi, A. Omlin and J. S. de Bono are employees of The Institute of Cancer Research, where abiraterone was first designed and synthesized and which has a commercial interest in abiraterone. J. S. de Bono has received consulting fees from Ortho Biotech Oncology Research and Development (a unit of Cougar Biotechnology), consulting fees and travel support from Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dendreon, Enzon, Exelixis, Genentech, GlaxoSmithKline, Medivation, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Supergen, and Takeda, and grant support from AstraZeneca.

Supplementary information

Supplementary Table 1

Ongoing clinical trials in chemotherapy-naive patients with CRPC (DOC 100 kb)

Supplementary Table 2

Ongoing clinical trials in CRPC previously treated with chemotherapy (DOC 75 kb)

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Yap, T., Zivi, A., Omlin, A. et al. The changing therapeutic landscape of castration-resistant prostate cancer. Nat Rev Clin Oncol 8, 597–610 (2011). https://doi.org/10.1038/nrclinonc.2011.117

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