The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity.
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity.
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DOI：
10.1038/nature11003
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发表时间：
2012-03-28
期刊：
影响因子：
64.8
通讯作者：
Garraway, Levi A.
中科院分区：
文献类型：
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作者：
Barretina, Jordi;Caponigro, Giordano;Stransky, Nicolas;Venkatesan, Kavitha;Margolin, Adam A.;Kim, Sungjoon;Wilson, Christopher J.;Lehar, Joseph;Kryukov, Gregory V.;Sonkin, Dmitriy;Reddy, Anupama;Liu, Manway;Murray, Lauren;Berger, Michael F.;Monahan, John E.;Morais, Paula;Meltzer, Jodi;Korejwa, Adam;Jane-Valbuena, Judit;Mapa, Felipa A.;Thibault, Joseph;Bric-Furlong, Eva;Raman, Pichai;Shipway, Aaron;Engels, Ingo H.;Cheng, Jill;Yu, Guoying K.;Yu, Jianjun;Aspesi, Peter, Jr.;de Silva, Melanie;Jagtap, Kalpana;Jones, Michael D.;Wang, Li;Hatton, Charles;Palescandolo, Emanuele;Gupta, Supriya;Mahan, Scott;Sougnez, Carrie;Onofrio, Robert C.;Liefeld, Ted;MacConaill, Laura;Winckler, Wendy;Reich, Michael;Li, Nanxin;Mesirov, Jill P.;Gabriel, Stacey B.;Getz, Gad;Ardlie, Kristin;Chan, Vivien;Myer, Vic E.;Weber, Barbara L.;Porter, Jeff;Warmuth, Markus;Finan, Peter;Harris, Jennifer L.;Meyerson, Matthew;Golub, Todd R.;Morrissey, Michael P.;Sellers, William R.;Schlegel, Robert;Garraway, Levi A.
将癌症基因组数据系统地转化为肿瘤生物学和治疗途径的知识仍然具有挑战性。这些努力应该得到强大的临床前模型系统的极大帮助，这些模型系统反映了人类癌症的基因组多样性，并且可以获得详细的遗传和药理学注释。在这里，我们描述了癌细胞系百科全书（CCLE）：基因表达，染色体拷贝数和大规模平行测序数据从947人类癌细胞系的汇编。当与479个品系中24种抗癌药物的药理学特征相结合时，该集合允许鉴定基于遗传、谱系和基因表达的药物敏感性预测因子。除了已知的预测因子外，我们还发现浆细胞谱系与对IGF 1受体抑制剂的敏感性相关; AHR表达与NRAS突变株中MEK抑制剂的疗效相关; SLFN 11表达可预测对拓扑异构酶抑制剂的敏感性。总之，我们的研究结果表明，大的，注释的细胞系集合可能有助于实现抗癌药物的临床前分层方案。在临床前环境中产生药物反应的遗传预测，并将其纳入癌症临床试验设计，可以加速“个性化”治疗方案的出现。
The systematic translation of cancer genomic data into knowledge of tumor biology and therapeutic avenues 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 pharmacologic annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number, and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacologic profiles for 24 anticancer drugs across 479 of the 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. Altogether, our results suggest 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.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
64.8
作者：
Solit, DB;Garraway, LA;Rosen, N
通讯作者：
Rosen, N
影响因子：
6.4
作者：
Muller, Christoph R.;Paulsen, Erik B.;Myklebost, Ola
通讯作者：
Myklebost, Ola
影响因子：
50.3
作者：
Neve, Richard M.;Chin, Koei;Gray, Joe W.
通讯作者：
Gray, Joe W.
DOI：
10.1093/jnci/91.22.1940
发表时间：
1999-11-17
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Kelland, LR;Sharp, SY;Workman, P
通讯作者：
Workman, P