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Canonical and Noncanonical Androgen Metabolism and Activity

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Prostate Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1210))

Abstract

Androgens are critical drivers of prostate cancer. In this chapter we first discuss the canonical pathways of androgen metabolism and their alterations in prostate cancer progression, including the classical, backdoor and 5α-dione pathways, the role of pre-receptor DHT metabolism, and recent findings on oncogenic splicing of steroidogenic enzymes. Next, we discuss the activity and metabolism of non-canonical 11-oxygenated androgens that can activate wild-type AR and are less susceptible to glucuronidation and inactivation than the canonical androgens, thereby serving as an under-recognized reservoir of active ligands. We then discuss an emerging literature on the potential non-canonical role of androgen metabolizing enzymes in driving prostate cancer. We conclude by discussing the potential implications of these findings for prostate cancer progression, particularly in context of new agents such as abiraterone and enzalutamide, which target the AR-axis for prostate cancer therapy, including mechanisms of response and resistance and implications of these findings for future therapy.

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Acknowledgement

NIH Pacific Northwest Prostate Cancer SPORE P50 CA97186

NIH P01 CA163227

Department of Defense CDMRP W81XWH-12-1-0208

Department of Veterans Affairs Puget Sound Health Care System

Damon Runyon Cancer Research Foundation (Damon Runyon-Genentech Clinical Investigator Award CI-40-08).

National Research Foundation of South Africa (CPRR 98886)

Medical Research Council of South Africa

Department of Defense CDMRP W81XWH-11-2-0154

Department of Defense CDMRP W81XWH-15-1-0150

Author information

Authors and Affiliations

  1. Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa

    Karl-Heinz Storbeck

  2. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Elahe A. Mostaghel

  3. Department of Medicine, University of Washington, Seattle, WA, USA

    Elahe A. Mostaghel

  4. Geriatric Research, Education and Clinical Center S-182, VA Puget Sound Health Care System, Seattle, WA, USA

    Elahe A. Mostaghel

Authors
  1. Karl-Heinz Storbeck
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  2. Elahe A. Mostaghel
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Correspondence to Elahe A. Mostaghel .

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Editors and Affiliations

  1. Department of Laboratory Medicine and Pathology, Department of Urology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Scott M. Dehm

  2. Departments of Urology, and Biochemistry & Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA

    Donald J. Tindall

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Storbeck, KH., Mostaghel, E.A. (2019). Canonical and Noncanonical Androgen Metabolism and Activity. In: Dehm, S., Tindall, D. (eds) Prostate Cancer. Advances in Experimental Medicine and Biology, vol 1210. Springer, Cham. https://doi.org/10.1007/978-3-030-32656-2_11

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