A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer

被引：1334

作者：

Berns, Katrien

Horlings, Hugo M.

Hennessy, Bryan T.

Madiredjo, Mandy

Hijmans, E. Marielle

Beelen, Karin

Linn, Sabine C.

Gonzalez-Angulo, Ana Maria

Stemke-Hale, Katherine

Hauptmann, Michael

Beijersbergen, Roderick L.

Mills, Gordon B.

de Vijver, Marc J. van

Bernards, Rene

机构：

[1] Netherlands Canc Inst, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

[2] Netherlands Canc Inst, Ctr Biomed Genet, NL-1066 CX Amsterdam, Netherlands

[3] Netherlands Canc Inst, Div Expt Therapy, NL-1066 CX Amsterdam, Netherlands

[4] Netherlands Canc Inst, Div Med Oncol, NL-1066 CX Amsterdam, Netherlands

[5] Netherlands Canc Inst, Div Mol Biol, NL-1066 CX Amsterdam, Netherlands

[6] Univ Texas, MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

来源：

CANCER CELL | 2007年 / 12卷 / 04期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.ccr.2007.08.030

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

A large-scale RNA interference screen to discover genes involved in trastuzumab resistance in breast cancer identified only PTEN as a modulator of drug sensitivity. Oncogenic mutants of PIK3CA (activator of the same pathway and frequently mutated in breast cancer) also conferred resistance to trastuzumab in cell culture. In a cohort of 55 breast cancer patients, activation of the PI3K pathway, as judged by the presence of oncogenic PIK3CA mutations or low PTEN expression, was associated with poor prognosis after trastuzumab therapy, and the combined analysis of PTEN and PIK3CA identified twice as many patients at increased risk for progression compared to PTEN alone. Thus, assessment of PI3K pathway activation may provide a biomarker to identify patients unlikely to respond to trastuzumab-based therapy.

引用

页码：395 / 402

页数：8

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