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.
N1 - Funding Information:
This publication has been funded in part by a Howard Hughes Medical Institute Physician-Scientist Early Career Award, the Prostate Cancer Foundation, an American Cancer Society Research Scholar Award (12-038-01-CCE), grant PC080193 from the U.S. Army Medical Research and Materiel Command, 1R01CA168899 and 1R01CA172382-01 from the National Institutes of Health, to NS.
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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U2 - 10.1038/bjc.2014.268
DO - 10.1038/bjc.2014.268
M3 - Review article
C2 - 24867689
AN - SCOPUS:84910013455
SN - 0007-0920
VL - 111
SP - 1249
EP - 1254
JO - British journal of cancer
JF - British journal of cancer
IS - 7
ER -