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Canonical and Noncanonical Androgen Metabolism and Activity

Karl-Heinz Storbeck1, Elahe A Mostaghel2,3,4

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

Advances in Experimental Medicine and Biology
|January 5, 2020
PubMed

Insights

Androgen metabolism pathways are altered in prostate cancer, with non-canonical androgens offering new therapeutic targets. Understanding these pathways is crucial for developing effective prostate cancer treatments.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Androgens are key drivers of prostate cancer (PCa) progression.
  • Canonical androgen metabolism pathways are well-studied but alterations occur during PCa.
  • Emerging evidence suggests non-canonical androgen pathways play a significant role.

Purpose of the Study:

  • To review canonical and non-canonical androgen metabolism in prostate cancer.
  • To explore the role of androgen metabolizing enzymes in PCa.
  • To discuss implications for current and future prostate cancer therapies.

Main Methods:

  • Review of existing literature on androgen metabolism and prostate cancer.
  • Analysis of canonical pathways (classical, backdoor, 5α-dione).
  • Examination of non-canonical 11-oxygenated androgens and their activity.

Main Results:

  • Alterations in canonical androgen metabolism pathways are observed in PCa.
  • Non-canonical 11-oxygenated androgens are active ligands, resistant to inactivation.
  • Androgen metabolizing enzymes may have non-canonical roles in driving PCa.

Conclusions:

  • Findings highlight the importance of diverse androgen metabolism pathways in PCa.
  • Understanding these pathways is critical for abiraterone and enzalutamide efficacy.
  • New therapeutic strategies targeting androgen metabolism are warranted for PCa treatment.
Keywords:
11-ketodihydrotestosterone11-ketotestosterone11β-hydroxyandrostenedioneAbirateroneAdrenal androgenAndrogen receptorCYP17A1Castration resistant prostate cancerDeoxycorticosteroneEnzalutamideIntracrinePrimary prostate cancerSplice variantSteroidogenesis

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