Hsp90: Still a viable target in prostate cancer

被引:41
作者
Centenera, Margaret M. [1 ,2 ,3 ]
Fitzpatrick, Alyssa K. [1 ,2 ,3 ]
Tilley, Wayne D. [1 ,2 ,3 ,4 ]
Butler, Lisa M. [1 ,2 ,3 ,4 ,5 ]
机构
[1] Univ Adelaide, Dame Roma Mitchell Canc Res Labs, Adelaide, SA 5000, Australia
[2] Univ Adelaide, Adelaide Prostate Canc Res Ctr, Adelaide, SA 5000, Australia
[3] Hanson Inst, Adelaide, SA 5000, Australia
[4] Univ Adelaide, Freemasons Fdn Ctr Mens Hlth, Adelaide, SA 5000, Australia
[5] Univ Adelaide, Ctr Personalised Canc Med, Adelaide, SA 5000, Australia
来源
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER | 2013年 / 1835卷 / 02期
基金
英国医学研究理事会;
关键词
Hsp90; Inhibitors; Prostate cancer; Clinical trials; SHOCK-PROTEIN; 90; PHASE-II TRIAL; POTENT ANTITUMOR-ACTIVITY; MOLECULAR CHAPERONE; ANDROGEN RECEPTOR; IN-VITRO; HYDROCHLORIDE IPI-504; INHIBITOR NVP-AUY922; INCREASED SURVIVAL; CARCINOMA-CELLS;
D O I
10.1016/j.bbcan.2012.12.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Heat shock protein 90 (Hsp90) is a molecular chaperone that regulates the maturation, activation and stability of critical signaling proteins that drive the development and progression of prostate cancer, including the androgen receptor. Despite robust predinical data demonstrating anti-tumor activity of first-generation Hsp90 inhibitors in prostate cancer, poor clinical responses initially cast doubt over the clinical utility of this class of agent. Recent advances in compound design and development, use of novel predinical models and further biological insights into Hsp90 structure and function have now stimulated a resurgence in enthusiasm for these drugs as a therapeutic option. This review highlights how the development of new-generation Hsp90 inhibitors with improved physical and pharmacological properties is unfolding, and discusses the potential contexts for their use either as single agents or in combination, for men with metastatic prostate cancer. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:211 / 218
页数:8
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