Androgen metabolism in prostate cancer: from molecular mechanisms to clinical consequences.

K. H. Chang, C. E. Ercole, N. Sharifi

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Despite our most vigorous efforts, prostate cancer remains the second leading cause of cancer death in men. Understanding the intricacies of androgen metabolism is vital to finding therapeutic targets, particularly with progression of advanced prostate cancer after initial hormone therapy, where adrenal precursors are involved. Such is the case with castration-resistant prostate cancer, where adrenal androgens, for example, dehydroepiandrosterone, are a source for intratumoural synthesis of dihydrotestosterone. As prostate cancer progresses, androgen metabolism changes due to altered expression of steroidogenic enzymes and mutations in the components of the steroidogenic machinery. These alterations sustain disease and allow progression; mechanistically, they may also enable development of hormone therapy resistance. With the development of the newer agents, abiraterone acetate and enzalutamide, efforts have been made to better define the basis for response and resistance. This work can be carried out in cell lines, animal models, as well as with ex vivo analysis of tissues obtained from patients. Efforts to further elucidate the finer details of the steroidogenic pathway are necessary to move toward a curative paradigm for patients with localised disease at high risk for recurrence.

Original languageEnglish (US)
Pages (from-to)1249-1254
Number of pages6
JournalBritish Journal of Cancer
Volume111
Issue number7
DOIs
StatePublished - 2014

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Androgens
Prostatic Neoplasms
Hormones
Dehydroepiandrosterone
Dihydrotestosterone
Castration
Disease Progression
Cause of Death
Therapeutics
Animal Models
Recurrence
Cell Line
Mutation
Enzymes
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Androgen metabolism in prostate cancer : from molecular mechanisms to clinical consequences. / Chang, K. H.; Ercole, C. E.; Sharifi, N.

In: British Journal of Cancer, Vol. 111, No. 7, 2014, p. 1249-1254.

Research output: Contribution to journalArticle

Chang, K. H. ; Ercole, C. E. ; Sharifi, N. / Androgen metabolism in prostate cancer : from molecular mechanisms to clinical consequences. In: British Journal of Cancer. 2014 ; Vol. 111, No. 7. pp. 1249-1254.
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