共 80 条
Clinical appraisal of abiraterone in the treatment of metastatic prostatic cancer: patient considerations, novel opportunities, and future directions
被引:12
作者:

Bedoya, Diego J.
论文数: 0 引用数: 0
h-index: 0
机构:
Clearview Canc Inst, Huntsville, AL USA Clearview Canc Inst, Huntsville, AL USA

Mitsiades, Nicholas
论文数: 0 引用数: 0
h-index: 0
机构:
Baylor Coll Med, Dept Med, Houston, TX 77030 USA
Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA Clearview Canc Inst, Huntsville, AL USA
机构:
[1] Clearview Canc Inst, Huntsville, AL USA
[2] Baylor Coll Med, Dept Med, Houston, TX 77030 USA
[3] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
来源:
ONCOTARGETS AND THERAPY
|
2013年
/
6卷
关键词:
androgen synthesis;
testosterone;
dihydrotestosterone;
CYP17;
AKR1C3;
MDV3100 (enzalutamide);
ANDROGEN RECEPTOR TRANSACTIVATION;
STEROIDOGENIC ENZYMES;
DIHYDROTESTOSTERONE LEVELS;
ANTIANDROGEN WITHDRAWAL;
CYP17A1;
INHIBITION;
INCREASED SURVIVAL;
PLUS PREDNISONE;
CASTRATION;
EXPRESSION;
ACETATE;
D O I:
10.2147/OTT.S24941
中图分类号:
Q81 [生物工程学(生物技术)];
Q93 [微生物学];
学科分类号:
071005 ;
0836 ;
090102 ;
100705 ;
摘要:
While androgen-deprivation therapy can induce dramatic clinical responses in advanced and metastatic prostate cancer, refractory disease (castration-resistant prostate cancer [CRPC]) eventually emerges. In recent years, several studies have demonstrated the importance of residual intratumoral androgens in maintaining androgen receptor (AR) transcriptional activity in CRPC. The cytochrome P450 enzyme CYP17 is an obligatory step in androgen synthesis, and therefore a critical therapeutic target in CRPC. Abiraterone acetate is a selective, irreversible inhibitor of CYP17 and can suppress adrenal synthesis of androgen precursors, and possibly in situ steroidogenesis in the tumor microenvironment. In a phase III multicenter study, abiraterone in combination with prednisone improved median overall survival of men with docetaxel-refractory CRPC by 3.9 months compared to placebo plus prednisone, and also resulted in higher objective prostate-specific antigen and radiographic response rates. The study led to the FDA approval in April 2011 of abiraterone for treatment of chemotherapy-refractory CRPC patients, validating steroidogenesis and the AR axis in general as therapeutic targets in CRPC. The FDA indication for abiraterone was expanded to all CRPCs in December 2012, while evaluation in even earlier disease states is ongoing. We propose a comprehensive AR axis-targeting approach via simultaneous, frontline enzymatic blockade of several steroidogenic enzymes (eg, CYP17 and AKR1C3) in combination with gonadotropin-releasing hormone analogs and potent, second-generation AR antagonists (eg, enzalutamide) in order to improve outcomes in patients with prostate cancer.
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页码:9 / 18
页数:10
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Mem Sloan Kettering Canc Ctr, Div Solid Tumor Oncol, Genitourinary Oncol Serv, New York, NY 10065 USA
Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA Mem Sloan Kettering Canc Ctr, Div Solid Tumor Oncol, Genitourinary Oncol Serv, New York, NY 10065 USA

Sawyers, Charles L.
论文数: 0 引用数: 0
h-index: 0
机构:
Mem Sloan Kettering Canc Ctr, Div Solid Tumor Oncol, Genitourinary Oncol Serv, New York, NY 10065 USA
Howard Hughes Med Inst, Chevy Chase, MD USA Mem Sloan Kettering Canc Ctr, Div Solid Tumor Oncol, Genitourinary Oncol Serv, New York, NY 10065 USA

Scher, Howard I.
论文数: 0 引用数: 0
h-index: 0
机构:
Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA Mem Sloan Kettering Canc Ctr, Div Solid Tumor Oncol, Genitourinary Oncol Serv, New York, NY 10065 USA
[10]
Anti-androgens and androgen-depleting therapies in prostate cancer: new agents for an established target
[J].
Chen, Yu
;
Clegg, Nicola J.
;
Scher, Howard I.
.
LANCET ONCOLOGY,
2009, 10 (10)
:981-991

Chen, Yu
论文数: 0 引用数: 0
h-index: 0
机构:
Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA
Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Dept Med, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10065 USA

Clegg, Nicola J.
论文数: 0 引用数: 0
h-index: 0
机构:
Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA
Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Dept Med, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10065 USA

Scher, Howard I.
论文数: 0 引用数: 0
h-index: 0
机构:
Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Dept Med, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10065 USA Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Dept Med, Sidney Kimmel Ctr Prostate & Urol Canc, New York, NY 10065 USA