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Molecular Mechanisms of Prostate Cancer Progression After Castration

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Management of Castration Resistant Prostate Cancer

Part of the book series: Current Clinical Urology ((CCU))

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Abstract

The dominant driver of malignant behavior for most prostate cancers is the androgen receptor (AR). AR signaling may act at the genesis of the disease to trigger the appearance of rearrangements between AR-regulated genes, such as TMPRSS2, and transcription factor genes, such as ERG, and in turn, the products of such fusion genes, now regulated by AR, function to prevent terminal differentiation and to promote invasive tumor growth and metastatic dissemination. Interference with AR function has served as the principal treatment for advanced prostate cancer for more than seven decades. However, despite the well-known benefits of androgen deprivation therapy, disease progression to castration-resistant prostate cancer (CRPC) has proven inevitable. CRPC appears to evolve via two major mechanisms: one with maintained AR signaling (AR “addiction”) and the other without (escape from AR “addiction”). In this chapter, the molecular features of AR “addicted” and non-AR “addicted” cancers will be reviewed.

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Authors and Affiliations

  1. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Suite 1100 Weinberg Building, 401 North Broadway Street, Baltimore, MD, 21287, USA

    William G. Nelson MD, PhD

  2. Department of Urology, Urology Research Laboratories, Johns Hopkins University, 600 N. Wolfe Street, Marburg Building, Room 121, Baltimore, MD, 21287, USA

    Kenneth J. Pienta MD

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Correspondence to Kenneth J. Pienta MD .

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  1. Department of Surgery, University of Montreal Hospital Center, Montreal, Québec, Canada

    Fred Saad

  2. Department of Oncology, The Johns Hopkins University, Baltimore, Maryland, USA

    Mario A. Eisenberger

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Nelson, W.G., Pienta, K.J. (2014). Molecular Mechanisms of Prostate Cancer Progression After Castration. In: Saad, F., Eisenberger, M. (eds) Management of Castration Resistant Prostate Cancer. Current Clinical Urology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1176-9_3

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