The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity

被引：5841

作者：

Barretina, Jordi ^{[1
,2
,3
]}

Caponigro, Giordano ^{[4
]}

Stransky, Nicolas ^{[1
]}

Venkatesan, Kavitha ^{[4
]}

Margolin, Adam A. ^{[1
]}

Kim, Sungjoon ^{[5
]}

Wilson, Christopher J. ^{[4
]}

Lehar, Joseph ^{[4
]}

Kryukov, Gregory V. ^{[1
]}

Sonkin, Dmitriy ^{[4
]}

Reddy, Anupama ^{[4
]}

Liu, Manway ^{[4
]}

Murray, Lauren ^{[1
]}

Berger, Michael F. ^{[1
]}

Monahan, John E. ^{[4
]}

Morais, Paula ^{[1
]}

Meltzer, Jodi ^{[4
]}

Korejwa, Adam ^{[1
]}

Jane-Valbuena, Judit ^{[1
,2
]}

Mapa, Felipa A. ^{[4
]}

Thibault, Joseph ^{[5
]}

Bric-Furlong, Eva ^{[4
]}

Raman, Pichai ^{[4
]}

Shipway, Aaron ^{[5
]}

Engels, Ingo H. ^{[5
]}

Cheng, Jill ^{[6
]}

Yu, Guoying K. ^{[6
]}

Yu, Jianjun ^{[6
]}

Aspesi, Peter, Jr. ^{[4
]}

de Silva, Melanie ^{[4
]}

Jagtap, Kalpana ^{[4
]}

Jones, Michael D. ^{[4
]}

Wang, Li ^{[4
]}

Hatton, Charles ^{[3
]}

Palescandolo, Emanuele ^{[3
]}

Gupta, Supriya ^{[1
]}

Mahan, Scott ^{[1
]}

Sougnez, Carrie ^{[1
]}

Onofrio, Robert C. ^{[1
]}

Liefeld, Ted ^{[1
]}

MacConaill, Laura ^{[3
]}

Winckler, Wendy ^{[1
]}

Reich, Michael ^{[1
]}

Li, Nanxin ^{[5
]}

Mesirov, Jill P. ^{[1
]}

Gabriel, Stacey B. ^{[1
]}

Getz, Gad ^{[1
]}

Ardlie, Kristin ^{[1
]}

Chan, Vivien ^{[6
]}

Myer, Vic E. ^{[4
]}

机构：

[1] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA

[4] Novartis Inst Biomed Res, Cambridge, MA 02139 USA

[5] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA

[6] Novartis Inst Biomed Res, Emeryville, CA 94608 USA

[7] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[8] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

NATURE | 2012年 / 483卷 / 7391期

关键词：

MALIGNANT-MELANOMA; INHIBITOR; KINASE; RECEPTOR; ANTAGONIST; EXPRESSION;

D O I：

10.1038/nature11003

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available(1). Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens(2).

引用

页码：603 / 607

页数：5

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