Altered states: selectively drugging the Hsp90 cancer chaperone

被引：170

作者：

Workman, P ^{[1
]}

机构：

[1] Inst Canc Res, Canc Res UK Ctr Canc Therapeut, Sutton SM2 5NG, Surrey, England

来源：

TRENDS IN MOLECULAR MEDICINE | 2004年 / 10卷 / 02期

关键词：

D O I：

10.1016/j.molmed.2003.12.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The molecular chaperone Hsp90 is an exciting cancer drug target. The first Hsp90 inhibitor to enter clinical trials - the geldanamycin derivative 17AAG - has recently demonstrated proof-of-concept for successful target modulation, with signs of therapeutic benefit. An important property of Hsp90 inhibitors is their ability to cause simultaneous, combinatorial blockade of multiple cancer-causing pathways by promoting the degradation of many oncogenic client proteins. However, the reason for therapeutic selectivity in cancer cells versus normal cells is unclear. New research now shows that Hsp90 exists in cancer cells in a heightened, activated state that is highly susceptible to inhibition by 17AAG.

引用

页码：47 / 51

页数：5

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