The Androgen Receptor in Prostate Cancer: Effect of Structure, Ligands and Spliced Variants on Therapy.
The Androgen Receptor in Prostate Cancer: Effect of Structure, Ligands and Spliced Variants on Therapy.
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DOI：
10.3390/biomedicines8100422
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发表时间：
2020-10-15
期刊：
影响因子：
4.7
通讯作者：
Ghosh PM
中科院分区：
文献类型：
--
作者：
Messner EA;Steele TM;Tsamouri MM;Hejazi N;Gao AC;Mudryj M;Ghosh PM
The androgen receptor (AR) plays a predominant role in prostate cancer (PCa) pathology. It consists of an N-terminal domain (NTD), a DNA-binding domain (DBD), a hinge region (HR), and a ligand-binding domain (LBD) that binds androgens, including testosterone (T) and dihydrotestosterone (DHT). Ligand binding at the LBD promotes AR dimerization and translocation to the nucleus where the DBD binds target DNA. In PCa, AR signaling is perturbed by excessive androgen synthesis, AR amplification, mutation, or the formation of AR alternatively spliced variants (AR-V) that lack the LBD. Current therapies for advanced PCa include androgen synthesis inhibitors that suppress T and/or DHT synthesis, and AR inhibitors that prevent ligand binding at the LBD. However, AR mutations and AR-Vs render LBD-specific therapeutics ineffective. The DBD and NTD are novel targets for inhibition as both perform necessary roles in AR transcriptional activity and are less susceptible to AR alternative splicing compared to the LBD. DBD and NTD inhibition can potentially extend patient survival, improve quality of life, and overcome predominant mechanisms of resistance to current therapies. This review discusses various small molecule and other inhibitors developed against the DBD and NTD—and the current state of the available compounds in clinical development.
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DOI：
10.1158/1078-0432.ccr-08-1402
发表时间：
2009-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Bedolla RG;Wang Y;Asuncion A;Chamie K;Siddiqui S;Mudryj MM;Prihoda TJ;Siddiqui J;Chinnaiyan AM;Mehra R;de Vere White RW;Ghosh PM
通讯作者：
Ghosh PM
影响因子：
2
作者：
Eisermann K;Wang D;Jing Y;Pascal LE;Wang Z
通讯作者：
Wang Z
影响因子：
3.9
作者：
Dehm SM;Tindall DJ
通讯作者：
Tindall DJ
影响因子：
5.4
作者：
Ahrens-Fath, I;Politz, O;Haendler, B
通讯作者：
Haendler, B
影响因子：
51.1
作者：
Chi, Kim N.;Protheroe, Andrew;Fizazi, Karim
通讯作者：
Fizazi, Karim