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

An Addendum to this article was published on 17 December 2018

An Addendum to this article was published on 28 November 2012


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 available1. 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 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 regimens2.

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Figure 1: The Cancer Cell Line Encyclopedia.
Figure 2: Predictive modelling of pharmacological sensitivity using CCLE genomic data.
Figure 3: AHR expression may denote a tumour dependency targeted by MEK inhibitors in NRAS-mutant cell lines.
Figure 4: Predicting sensitivity to topoisomerase I inhibitors.

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Accession codes

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Gene Expression Omnibus

Data deposits

Data have been deposited in the Gene ExpressionOmnibus (GEO) using accession number GSE36139 and are also available at


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We thank the staff of the Biological Samples Platform, the Genetic Analysis Platform and the Sequencing Platform at the Broad Institute. We thank S. Banerji, J. Che, C .M. Johannessen, A. Su and N. Wagle for advice and discussion. We are grateful for the technical assistance and support of G. Bonamy, R. Brusch III, E. Gelfand, K. Gravelin, T. Huynh, S. Kehoe, K. Matthews, J. Nedzel, L. Niu, R. Pinchback, D. Roby, J. Slind, T. R. Smith, L. Tan, V. Trinh, C. Vickers, G. Yang, Y. Yao and X. Zhang. The Cancer Cell Line Encyclopedia project was enabled by a grant from the Novartis Institutes for Biomedical Research. Additional funding support was provided by the National Cancer Institute (M.M., L.A.G.), the Starr Cancer Consortium (M.F.B., L.A.G.), and the NIH Director’s New Innovator Award (L.A.G.).

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Authors and Affiliations



For the work described herein, J.B. and G.C. were the lead research scientists; N.S., K.V. and A.M.M. were the lead computational biologists; M.P.M., W.R.S., R.S. and L.A.G. were the senior authors. J.B., G.C., S.K., P.M., J.M., J.T., A.S., N.L. and K.A. performed cell-line procural and processing; P.M. and K.A. performed or directed nucleic acid extraction and quality control; S.G., W.W. and S.B.G. performed or directed genomic data generation; C.J.W., F.A.M., E.B.-F., I.H.E., P.A., M.d.S., K.J. and V.E.M. performed pharmacological data generation; N.S., K.V., G.V.K., A.R., M.F.B., J.C., G.K.Y., M.D.J., T.L., M.R. and G.G. contributed to software development; N.S., K.V., A.A.M., J.L., G.V.K., D.S., A.R., M.L., M.F.B., A.K., P.R., J.C., G.K.Y., J.Y., M.D.J., L.W., C.H., E.P., J.P.M., V.C. and M.P.M. performed computational biology and bioinformatics analysis; J.B., G.C., N.S., L.M., J.E.M., J.J.-V., M.P.M., W.R.S., R.S. and L.A.G. performed biological analysis and interpretation; N.S., K.V., A.A.M., J.L., A.R., M.L., L.M., A.K., J.J.-V., J.C., G.K.Y. and J.Y. prepared figures and tables for the main text and Supplementary Information; J.B., G.C., N.S., K.V., A.A.M., J.L., G.V.K., J.J.-V., M.P.M. and L.A.G. wrote and edited the main text and Supplementary Information; J.B., G.C., N.S., K.V., S.K., C.J.W., J.L., S.M., C.S., R.C.O., T.L., L.McC., W.W., M.R., N.L., S.B.G., K.A. and V.C. performed project management; J.P.M., V.E.M., B.L.W., J.P., M.W., P.F., J.L.H., M.M. and T.R.G. contributed project oversight and advisory roles; and M.P.M., W.R.S., R.S. and L.A.G. provided overall project leadership.

Corresponding authors

Correspondence to Robert Schlegel or Levi A. Garraway.

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Competing interests

Multiple authors are employees of Novartis, Inc., as noted in the affiliations. T.R.G., M.M. and L.A.G. are consultants for and equity holders in Foundation Medicine, Inc. M.M. and L.A.G. are consultants for and receive sponsored research from Novartis, Inc.

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Supplementary Information 1

This file contains Supplementary Figures 1-15 and legends for Supplementary Tables 1-12 (see separate file for Supplementary Tables). (PDF 5034 kb)

Supplementary Information 2

This file contains Supplementary Methods and additional references. (PDF 450 kb)

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This file contains Supplementary Tables 1-12 – see Supplementary Information 1 for legends. (XLS 5774 kb)

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Barretina, J., Caponigro, G., Stransky, N. et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483, 603–607 (2012).

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