TY - JOUR
T1 - Standard androgen deprivation therapy for prostate cancer
AU - Sharifi, Nima
N1 - Funding Information:
This publication has been funded in part by a Howard Hughes Medical Institute Physician-Scientist Early Career Award, a Prostate Cancer Foundation Award and from grant number PC080193 from the U.S. Army Medical Research and Materiel Command.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2010
Y1 - 2010
N2 - Prostate cancer is the second leading cause of cancer death for men in the United States. Tumor progression is driven by conversion of testosterone by 5a-reductase to dihydrotestosterone, which both bind and activate the androgen receptor (AR). Androgen deprivation therapy (ADT), or depletion of gonadal testosterone, blocks this sequence of events, and has been the mainstay of upfront systemic treatment for prostate cancer for 70 years. ADT is achieved by surgical or pharmacological means. Although the majority of circulating testosterone is depleted, intratumoral testosterone and dihydrotestosterone persist after ADT, implying the existence of alternative source(s) of these androgens. Importantly, the generation of intratumoral androgens and ensuing AR activation is a major mechanism that drives resistance to ADT. The goal of this review is to summarize the approaches to ADT, effects on the tumor, clinical benefits and mechanisms of resistance.
AB - Prostate cancer is the second leading cause of cancer death for men in the United States. Tumor progression is driven by conversion of testosterone by 5a-reductase to dihydrotestosterone, which both bind and activate the androgen receptor (AR). Androgen deprivation therapy (ADT), or depletion of gonadal testosterone, blocks this sequence of events, and has been the mainstay of upfront systemic treatment for prostate cancer for 70 years. ADT is achieved by surgical or pharmacological means. Although the majority of circulating testosterone is depleted, intratumoral testosterone and dihydrotestosterone persist after ADT, implying the existence of alternative source(s) of these androgens. Importantly, the generation of intratumoral androgens and ensuing AR activation is a major mechanism that drives resistance to ADT. The goal of this review is to summarize the approaches to ADT, effects on the tumor, clinical benefits and mechanisms of resistance.
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U2 - 10.1016/j.ddstr.2011.02.002
DO - 10.1016/j.ddstr.2011.02.002
M3 - Review article
AN - SCOPUS:80055001129
SN - 1740-6773
VL - 7
SP - 5
EP - 8
JO - Drug Discovery Today: Therapeutic Strategies
JF - Drug Discovery Today: Therapeutic Strategies
IS - 1-2
ER -