Abstract
Androgen deprivation therapy remains a critical component of treatment for men with advanced prostate cancer, and data support its use in metastatic disease and in conjunction with surgery or radiation in specific settings. Alternatives to standard androgen deprivation therapy, such as intermittent androgen suppression and estrogen therapy, hold the potential to improve toxicity profiles while maintaining clinical benefit. Current androgen deprivation strategies seem to incompletely suppress androgen levels and androgen-receptor-mediated effects at the tissue level. Advances in the understanding of mechanisms that contribute to castration-resistant prostate cancer are leading to rationally designed therapies targeting androgen metabolism and the androgen receptor. The results of large trials investigating the optimization of primary androgen deprivation therapy, including evaluation of intermittent androgen suppression and phase III studies of novel androgen synthesis inhibitors, such as abiraterone acetate, are eagerly awaited.
Key Points
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Androgen deprivation therapy remains a critical component of treatment in men with advanced prostate cancer, and data supports its use in metastatic disease and in conjunction with surgery or radiation therapy in specific settings
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Alternatives to standard androgen deprivation therapy, such as intermittent androgen suppression and estrogen therapy, hold the potential to improve toxicity profiles while maintaining clinical benefit
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Current androgen deprivation strategies seem to incompletely suppress androgen levels and AR-mediated effects at the tissue level
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Multiple mechanisms are implicated in the development of castration resistance, but the majority involve continued activation of the AR, which might be targeted by novel therapeutic agents
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Acknowledgements
This work was made possible by funding through the NIH/NCI Pacific Northwest Prostate Cancer SPORE grant P50CA97186 (to PS Nelson and B Montgomery) and the Kirschstein-NRSA T32 training grant (to WP Harris).Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.
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PS Nelson has declared that he has acted as a consultant and received grant/research support from GlaxoSmithKline.
B Montgomery had declared that he has received grant/research support from Cougar Biotechnology.
WP Harris and EA Mostaghel declared no competing interests.
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Harris, W., Mostaghel, E., Nelson, P. et al. Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion. Nat Rev Urol 6, 76–85 (2009). https://doi.org/10.1038/ncpuro1296
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DOI: https://doi.org/10.1038/ncpuro1296
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