Molecular processes leading to aberrant androgen receptor signaling and castration resistance in prostate cancer

被引:41
作者
Hu, Rong [1 ]
Denmeade, Samuel R. [2 ]
Luo, Jun [1 ]
机构
[1] Johns Hopkins Univ, 600 North Wolfe St,411 Marburg Bldg, Baltimore, MD 21287 USA
[2] Canc Res Bldg, Baltimore, MD USA
关键词
androgen receptor; AR; AR signaling; AR splicing variants; castration-resistant prostate cancer; CRPC; hormone therapy; prostate cancer;
D O I
10.1586/EEM.10.49
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Hormone therapies targeting androgen receptor signaling are the mainstay of treatment for patients with advanced prostate cancer. The length of clinical remission induced by hormone therapies varies substantially among treated patients. Why some patients progress rapidly after treatment while others benefit with prolonged remission is a question that remains unsolved. The androgen receptor signaling pathway is the key molecular determinant of castration resistance, and a key target for prostate cancer drug design. Recent advances in characterizing molecular processes leading to the development of castration-resistant prostate cancer, including the discovery of multiple androgen receptor splicing variants, offer opportunities for rational development of new clinical tools or approaches to predict, monitor or control/prevent prostate cancer progression in the castrate setting.
引用
收藏
页码:753 / 764
页数:12
相关论文
共 133 条
[41]   COMPARISON OF PROSTATIC-CANCER TISSUE DIHYDROTESTOSTERONE LEVELS AT THE TIME OF RELAPSE FOLLOWING ORCHIECTOMY OR ESTROGEN THERAPY [J].
GELLER, J ;
ALBERT, JD ;
NACHTSHEIM, DA ;
LOZA, D .
JOURNAL OF UROLOGY, 1984, 132 (04) :693-696
[42]   Molecular biology of the androgen receptor [J].
Gelmann, EP .
JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (13) :3001-3015
[43]   The prognostic significance of plasma interleukin-6 levels in patients with metastatic hormone-refractory prostate cancer: Results from cancer and leukemia group B 9480 [J].
George, DJ ;
Halabi, S ;
Shepard, TF ;
Sanford, B ;
Vogelzang, NJ ;
Small, EJ ;
Kantoff, PW .
CLINICAL CANCER RESEARCH, 2005, 11 (05) :1815-1820
[44]   Androgen receptor phosphorylation - Regulation and identification of the phosphorylation sites. [J].
Gioeli, D ;
Ficarro, SB ;
Kwiek, JJ ;
Aaronson, D ;
Hancock, M ;
Catling, AD ;
White, FM ;
Christian, RE ;
Settlage, RE ;
Shabanowitz, J ;
Hunt, DF ;
Weber, MJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (32) :29304-29314
[45]  
Gleave M, 1999, CLIN CANCER RES, V5, P2891
[46]   The androgen receptor gene mutations database (ARDB): 2004 update [J].
Gottlieb, B ;
Beitel, LK ;
Wu, JH ;
Trifiro, M .
HUMAN MUTATION, 2004, 23 (06) :527-533
[47]   Increased AKT activity contributes to prostate cancer progression by dramatically accelerating prostate tumor growth and diminishing p27Kip1 expression [J].
Graff, JR ;
Konicek, BW ;
McNulty, AM ;
Wang, ZJ ;
Houck, K ;
Allen, S ;
Paul, JD ;
Hbaiu, A ;
Goode, RG ;
Sandusky, GE ;
Vessella, RL ;
Neubauer, BL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (32) :24500-24505
[48]   Epidermal growth factor increases coactivation of the androgen receptor in recurrent prostate cancer [J].
Gregory, CW ;
Fei, XY ;
Ponguta, LA ;
He, B ;
Bill, HM ;
French, FS ;
Wilson, EM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (08) :7119-7130
[49]  
Gregory CW, 2001, CANCER RES, V61, P4315
[50]   Regulation of androgen receptor activity by tyrosine phosphorylation [J].
Guo, Zhiyong ;
Dai, Bojie ;
Jiang, Tianyun ;
Xu, Kexin ;
Xie, Yingqiu ;
Kim, Oekyung ;
Nesheiwat, Issa ;
Kong, Xiangtian ;
Melamed, Jonathan ;
Handratta, Venkatesh D. ;
Njar, Vincent C. O. ;
Brodie, Angela M. H. ;
Yu, Li-Rong ;
Veenstra, Timothy D. ;
Chen, Hegang ;
Qiu, Yun .
CANCER CELL, 2006, 10 (04) :309-319