Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises

被引：463

作者：

Yap, Timothy A. ^{[1
,3
]}

Garrett, Michelle D. ^{[1
]}

Walton, Mike I. ^{[1
]}

Raynaud, Florence ^{[1
]}

de Bono, Johann S. ^{[2
,3
]}

Workman, Paul ^{[1
]}

机构：

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

[2] Inst Canc Res, Med Sect, Sutton SM2 5NG, Surrey, England

[3] Royal Marsden NHS Fdn Trust, Sutton SM2 5PT, Surrey, England

来源：

CURRENT OPINION IN PHARMACOLOGY | 2008年 / 8卷 / 04期

关键词：

D O I：

10.1016/j.coph.2008.08.004

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The strategy of 'drugging the cancer kinome' has led to the successful development and regulatory approval of several novel molecular targeted agents. The spotlight is now shifting to the phosphatidylinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway as a key potential target. This review details the role of the pathway in oncogenesis and the rationale for inhibiting its vital components. The focus will be on the progress made in the development of novel therapies for cancer treatment, with emphasis placed on agents that have entered clinical development. Strategies involving horizontal and vertical blockade of the pathway, as well as the use of biomarkers to select appropriate patients and to provide proof of target modulation will also be highlighted. Finally, we discuss the issues and limitations involved with targeting the PI3K-AKT-mTOR pathway, and predict what the future may hold for these novel anticancer therapeutics.

引用

页码：393 / 412

页数：20

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