HSP90 inhibition: two-pronged exploitation of cancer dependencies

被引：81

作者：

Travers, Jon ^{[1
]}

Sharp, Swee ^{[1
]}

Workman, Paul ^{[1
]}

机构：

[1] Inst Canc Res, Signal Transduct & Mol Pharmacol Team, Canc Res UK Canc Therapeut Unit, Div Canc Therapeut,Haddow Labs, Sutton SM2 5NG, Surrey, England

来源：

DRUG DISCOVERY TODAY | 2012年 / 17卷 / 5-6期

基金：

英国医学研究理事会;

关键词：

SHOCK-PROTEIN; 90; PHASE-II TRIAL; TRANSCRIPTION FACTOR HSF1; HEAT-SHOCK; BREAST-CANCER; INDUCED APOPTOSIS; ATP-BINDING; IN-VITRO; CHAPERONE INHIBITORS; TANESPIMYCIN; 17-AAG;

D O I：

10.1016/j.drudis.2011.12.021

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The early clinical hypothesis for inhibiting HSP90 in cancers was based on the dependence of certain key client proteins in malignant cells - including a host of well-characterized oncoproteins - on the activity of HSP90 for their function and stability. The additional concept has been established that cancer cells have heightened dependence on the efficient maintenance of intracellular proteomic homeostasis, central components of which are HSP90 and other heat shock proteins. We evaluate the evidence that inhibiting HSP90 in cancer exploits both of these biological vulnerabilities very effectively, we review the current status of the discovery and development of HSP90 inhibitors and we identify routes to improve their clinical efficacy, based on emerging knowledge.

引用

页码：242 / 252

页数：11

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