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Advanced prostate cancer—a case for adjuvant differentiation therapy

Nature Reviews Urology volume 9, pages 595–602 (2012)Cite this article

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Abstract

The development of novel therapies such as abiraterone acetate and sipuleucel-T has improved the outlook for patients with advanced-stage and castration-resistant prostate cancer. However, the beneficial effects of these drugs are only measured in months. Moreover, the National Institute for Health and Clinical Excellence in the UK had ruled that the use of abiraterone acetate was not cost-effective before cost revision by the manufacturers. The FDA statement asserting that the use of 5α-reductase inhibitors for prostate cancer chemoprevention could increase the risk of developing high-grade prostate cancer also indirectly questions the value of direct androgen response manipulation for long-term benefit. These reports illustrate the need for a fresh and comprehensive analysis of advanced prostate cancer pathology to promote the next generation of effective adjuvant therapies. One such avenue is that of differentiation therapy, which seeks to promote the differentiation of cancer stem cells into a phenotype more sensitive to anticancer therapy than their parents. Using differentiation therapy with current antiandrogen therapies should augment our armoury of treatment for the management of advanced prostate cancer.

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Figure 1: Epithelial hierarchy within prostate cancer.
Figure 2: Current approach for identifying targets and the need to consider cellular heterogeneity in the normal and cancerous prostate.
Figure 3: Combination of current therapies and differentiation therapy for the management of advanced-stage prostate cancer.

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Acknowledgements

We would like to thank Dr Fiona Frame and Dr Euan Polson for their critical reading of the manuscript before submission. We would also like to acknowledge our funding from the EU Marie Curie Network: Prostate Research Organizations–Network of Early Stage Training (J. K. Rane), The Freemasons' Grand Charity (D. Pellacani) and Yorkshire Cancer Research (Project grant Y256 and Program grant) (D. Pellacani, N. J. Maitland).

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  1. Department of Biology (Area 13), Yorkshire Cancer Research Unit, University of York, York, YO10 5DD, UK

    Jayant K. Rane, Davide Pellacani & Norman J. Maitland

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J. K. Rane and D. Pellacani researched the data for and wrote the article. All authors contributed substantially to the discussion of the article content and edited the manuscript before submission.

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Correspondence to Norman J. Maitland.

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Rane, J., Pellacani, D. & Maitland, N. Advanced prostate cancer—a case for adjuvant differentiation therapy. Nat Rev Urol 9, 595–602 (2012). https://doi.org/10.1038/nrurol.2012.157

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