Abstract
To improve future drug development and patient management for patients with castration-resistant prostate cancer (CRPC), surrogate biomarkers that are linked to relevant outcomes are urgently needed. A biomarker must be measurable, reproducible, linked to relevant clinical outcomes, and demonstrate clinical utility. This area is rapidly evolving, with recent trials in patients with CRPC incorporating the detection of circulating tumour cells (CTCs), imaging, and patient-reported outcome biomarkers. We discuss the framework for the development of biomarkers for CRPC, including different categories and contexts of use. We also highlight the requirements of analytical validation, the sequence of trials needed for clinical validation and regulatory approval, and the future outlook for imaging and CTC biomarkers.
Key Points
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Improving current treatment for patients with castration-resistant prostate cancer requires new biomarkers and surrogate end points for clinical trials
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Of highest priority are biomarkers that reflect clinical benefit, and predictive biomarkers to guide the selection of treatment most likely to work in the individual patient
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The development and approval processes for biomarkers are rigorous and lengthy, requiring analytically valid assays and a sequence of trials that support the use of a biomarker in a specific context
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The investment of resources and time will be recovered by achieving streamlined clinical trials and better selection of new therapies for development
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Promising emerging biomarkers for castration-resistant prostate cancer include circulating tumour cells and new methods for imaging bone metastases
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Change history
12 March 2013
In the version of this article initially published online, the author contributions statement was incorrect and did not accredit the contribution of Howard I. Scher appropriately. The contributions statement has now been corrected.
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Acknowledgements
The work in this article was supported by: The Sidney Kimmel Center for Prostate and Urologic Cancers. Supported in part by the MSKCC SPORE in Prostate Cancer (P50 CA92629), the Department of Defense Prostate Cancer Research Program (PC051382), The Research and Therapeutics Program for Prostate Cancer, The Prostate Cancer Foundation, William H. and Alice Goodwin and the Commonwealth Foundation for Cancer Research and the Experimental Therapeutics Center of Memorial Sloan–Kettering Cancer Center (MSKCC). In addition, S. Larson was supported by P50 CA85438. We thank Amy Plofker, MSKCC editor, for manuscript editing.
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H. I. Scher devised the concept of the article, researched the data for the article, and co-wrote the article with M. J. Morris, S. Larson and G. Heller. All authors made a substantial contribution to discussion of the content, reviewed and edited the manuscript prior to submission, and revised the article after peer review.
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H. I. Scher is a consultant for Bristol-Myers Squibb, Dendreon, Endo/Orion Pharmaceuticals, Genentech, Novartis, Ortho Biotech Oncology Research & Development, and Sanofi Aventis. He receives research funding from Aragon, Bristol-Myers Squibb, Exelixis, Janssen Research & Development, Janssen Services, and Medivation. M. J. Morris is a consultant for Millennium. He receives research funding from Agensys, Algeta, Bayer, Genta, Medivation, and Sanofi Aventis. S. Larson is a consultant for ImaginAb, Perceptive, and Progenics. He receives research funding from GE Medical Systems. G. Heller declares no competing interests.
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Scher, H., Morris, M., Larson, S. et al. Validation and clinical utility of prostate cancer biomarkers. Nat Rev Clin Oncol 10, 225–234 (2013). https://doi.org/10.1038/nrclinonc.2013.30
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DOI: https://doi.org/10.1038/nrclinonc.2013.30
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