Targeting the Androgen Signaling Axis in Prostate Cancer

被引：76

作者：

Dai, Charles ^{[1
,2
,3
]}

Dehm, Scott M. ^{[4
,5
,6
]}

Sharifi, Nima ^{[7
,8
,9
,10
,11
,12
]}

机构：

[1] Massachusetts Gen Hosp, Canc Ctr, Boston, MA USA

[2] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA

[3] Dana Farber Canc Inst, Boston, MA USA

[4] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN USA

[5] Univ Minnesota, Dept Urol, Minneapolis, MN USA

[6] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA

[7] Cleveland Clin, Lerner Res Inst, Genitourinary Malignancies Res Ctr, Cleveland, OH USA

[8] Cleveland Clin, Glickman Urol & Kidney Inst, Dept Urol, Cleveland, OH USA

[9] Cleveland Clin, Taussig Canc Inst, Dept Hematol Oncol, Cleveland, OH USA

[10] Univ Miami, Miller Sch Med, Desai Sethi Urol Inst, Miami, FL USA

[11] Univ Miami, Sylvester Comprehens Canc Ctr, Miller Sch Med, Miami, FL USA

[12] Univ Miami, Desai Sethi Urol Inst, Miller Sch Med, 1600 NW 10th Ave,6026 Rosenstiel Med Sci Bldg, Miami, FL 33136 USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2023年 / 41卷 / 26期

关键词：

STEROID-BINDING CHARACTERISTICS; RECEPTOR GENE; DEPRIVATION THERAPY; TRANSCRIPTIONAL ACTIVATION; INCREASED SURVIVAL; CLINICAL-OUTCOMES; DNA-REPAIR; PHASE-II; IN-VITRO; CASTRATION;

D O I：

10.1200/JCO.23.00433

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Activation of the androgen receptor (AR) and AR-driven transcriptional programs is central to the pathophysiology of prostate cancer. Despite successful translational efforts in targeting AR, therapeutic resistance often occurs as a result of molecular alterations in the androgen signaling axis. The efficacy of next-generation AR-directed therapies for castration-resistant prostate cancer has provided crucial clinical validation for the continued dependence on AR signaling and introduced a range of new treatment options for men with both castration-resistant and castration-sensitive disease. Despite this, however, metastatic prostate cancer largely remains an incurable disease, highlighting the need to better understand the diverse mechanisms by which tumors thwart AR-directed therapies, which may inform new therapeutic avenues. In this review, we revisit concepts in AR signaling and current understandings of AR signaling-dependent resistance mechanisms as well as the next frontier of AR targeting in prostate cancer.

引用

页码：4267 / +

页数：13

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