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 language | English (US) |
|---|---|
| Pages (from-to) | 1249-1254 |
| Number of pages | 6 |
| Journal | British Journal of Cancer |
| Volume | 111 |
| Issue number | 7 |
| DOIs | |
| State | Published - 2014 |
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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 journal › Article
}
TY - JOUR
T1 - Androgen metabolism in prostate cancer
T2 - from molecular mechanisms to clinical consequences.
AU - Chang, K. H.
AU - Ercole, C. E.
AU - Sharifi, N.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84910013455&partnerID=8YFLogxK
U2 - 10.1038/bjc.2014.268
DO - 10.1038/bjc.2014.268
M3 - Article
C2 - 24867689
AN - SCOPUS:84910013455
VL - 111
SP - 1249
EP - 1254
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 7
ER -