The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity (original) (raw)
Accession codes
Primary accessions
Gene Expression Omnibus
Data deposits
Data have been deposited in the Gene ExpressionOmnibus (GEO) using accession number GSE36139 and are also available at http://www.broadinstitute.org/ccle.
References
- Caponigro, G. & Sellers, W. R. Advances in the preclinical testing of cancer therapeutic hypotheses. Nature Rev. Drug Discov. 10, 179–187 (2011)
Article CAS Google Scholar - MacConaill, L. E. & Garraway, L. A. Clinical implications of the cancer genome. J. Clin. Oncol. 28, 5219–5228 (2010)
Article Google Scholar - Lin, W. M. et al. Modeling genomic diversity and tumor dependency in malignant melanoma. Cancer Res. 68, 664–673 (2008)
Article CAS Google Scholar - Neve, R. M. et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 10, 515–527 (2006)
Article CAS Google Scholar - Sos, M. L. et al. Predicting drug susceptibility of non-small cell lung cancers based on genetic lesions. J. Clin. Invest. 119, 1727–1740 (2009)
Article CAS Google Scholar - Dry, J. R. et al. Transcriptional pathway signatures predict MEK addiction and response to selumetinib (AZD6244). Cancer Res. 70, 2264–2273 (2010)
Article CAS Google Scholar - Garraway, L. A. et al. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 436, 117–122 (2005)
Article ADS CAS Google Scholar - Greshock, J. et al. Molecular target class is predictive of in vitro response profile. Cancer Res. 70, 3677–3686 (2010)
Article CAS Google Scholar - McDermott, U. et al. Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling. Proc. Natl Acad. Sci. USA 104, 19936–19941 (2007)
Article ADS CAS Google Scholar - Solit, D. B. et al. BRAF mutation predicts sensitivity to MEK inhibition. Nature 439, 358–362 (2006)
Article ADS CAS Google Scholar - Staunton, J. E. et al. Chemosensitivity prediction by transcriptional profiling. Proc. Natl Acad. Sci. USA 98, 10787–10792 (2001)
Article ADS CAS Google Scholar - Weinstein, J. N. et al. An information-intensive approach to the molecular pharmacology of cancer. Science 275, 343–349 (1997)
Article CAS Google Scholar - Thomas, R. K. et al. High-throughput oncogene mutation profiling in human cancer. Nature Genet. 39, 347–351 (2007)
Article CAS Google Scholar - Beroukhim, R. et al. The landscape of somatic copy-number alteration across human cancers. Nature 463, 899–905 (2010)
Article ADS CAS Google Scholar - Ross, D. T. et al. Systematic variation in gene expression patterns in human cancer cell lines. Nature Genet. 24, 227–235 (2000)
Article CAS Google Scholar - Zou, H. & Hastie, T. Regularization and variable selection via the elastic net. J. R. Stat. Soc. B 67, 301–320 (2005)
Article MathSciNet Google Scholar - Konecny, G. E. et al. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res. 66, 1630–1639 (2006)
Article CAS Google Scholar - Tsai, J. et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc. Natl Acad. Sci. USA 105, 3041–3046 (2008)
Article ADS CAS Google Scholar - Zou, H. Y. et al. An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res. 67, 4408–4417 (2007)
Article CAS Google Scholar - Müller, C. R. et al. Potential for treatment of liposarcomas with the MDM2 antagonist Nutlin-3A. Int. J. Cancer 121, 199–205 (2007)
Article Google Scholar - Nishio, M. et al. Serum heparan sulfate concentration is correlated with the failure of epidermal growth factor receptor tyrosine kinase inhibitor treatment in patients with lung adenocarcinoma. J. Thorac. Oncol. 6, 1889–1894 (2011)
Article Google Scholar - Guo, W. et al. Formation of 17-allylamino-demethoxygeldanamycin (17-AAG) hydroquinone by NAD(P)H:quinone oxidoreductase 1: role of 17-AAG hydroquinone in heat shock protein 90 inhibition. Cancer Res. 65, 10006–10015 (2005)
Article CAS Google Scholar - Kelland, L. R., Sharp, S. Y., Rogers, P. M., Myers, T. G. & Workman, P. DT-Diaphorase expression and tumor cell sensitivity to 17-allylamino, 17-demethoxygeldanamycin, an inhibitor of heat shock protein 90. J. Natl Cancer Inst. 91, 1940–1949 (1999)
Article CAS Google Scholar - Moreau, P. et al. Phase I study of the anti insulin-like growth factor 1 receptor (IGF-1R) monoclonal antibody, AVE1642, as single agent and in combination with bortezomib in patients with relapsed multiple myeloma. Leukemia 25, 872–874 (2011)
Article CAS Google Scholar - Reiners, J. J., Jr, Lee, J. Y., Clift, R. E., Dudley, D. T. & Myrand, S. P. PD98059 is an equipotent antagonist of the aryl hydrocarbon receptor and inhibitor of mitogen-activated protein kinase kinase. Mol. Pharmacol. 53, 438–445 (1998)
Article CAS Google Scholar - Wagner, L. M. et al. Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma. Pediatr. Blood Cancer 48, 132–139 (2007)
Article Google Scholar - Garnett, M. J. et al. Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature http://dx.doi.org/10.1038/nature11005 (this issue)
Acknowledgements
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.).
Author information
Author notes
- Jordi Barretina, Adam A. Margolin & Michael F. Berger
Present address: Present addresses: Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA (J.B.); Sage Bionetworks, 1100 Fairview Ave. N., Seattle, Washington 98109, USA (A.A.M.); Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA (M.F.B.)., - Jordi Barretina, Giordano Caponigro, Nicolas Stransky, Kavitha Venkatesan, Adam A. Margolin, Michael P. Morrissey, William R. Sellers, Robert Schlegel and Levi A. Garraway: These authors contributed equally to this work.
Authors and Affiliations
- The Broad Institute of Harvard and MIT, Cambridge, 02142, Massachusetts, USA
Jordi Barretina, Nicolas Stransky, Adam A. Margolin, Gregory V. Kryukov, Lauren Murray, Michael F. Berger, Paula Morais, Adam Korejwa, Judit Jané-Valbuena, Supriya Gupta, Scott Mahan, Carrie Sougnez, Robert C. Onofrio, Ted Liefeld, Wendy Winckler, Michael Reich, Jill P. Mesirov, Stacey B. Gabriel, Gad Getz, Kristin Ardlie, Matthew Meyerson, Todd R. Golub & Levi A. Garraway - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, 02115, Massachusetts, USA
Jordi Barretina, Judit Jané-Valbuena, Matthew Meyerson & Levi A. Garraway - Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Harvard Medical School, Boston, 02115, Massachusetts, USA
Jordi Barretina, Charles Hatton, Emanuele Palescandolo, Laura MacConaill, Matthew Meyerson, Todd R. Golub & Levi A. Garraway - Novartis Institutes for Biomedical Research, Cambridge, 02139, Massachusetts, USA
Giordano Caponigro, Kavitha Venkatesan, Christopher J. Wilson, Joseph Lehár, Dmitriy Sonkin, Anupama Reddy, Manway Liu, John E. Monahan, Jodi Meltzer, Felipa A. Mapa, Eva Bric-Furlong, Pichai Raman, Peter Aspesi, Melanie de Silva, Kalpana Jagtap, Michael D. Jones, Li Wang, Vic E. Myer, Barbara L. Weber, Jeff Porter, Markus Warmuth, Peter Finan, Michael P. Morrissey, William R. Sellers & Robert Schlegel - Genomics Institute of the Novartis Research Foundation, San Diego, 92121, California, USA
Sungjoon Kim, Joseph Thibault, Aaron Shipway, Ingo H. Engels, Nanxin Li & Jennifer L. Harris - Novartis Institutes for Biomedical Research, Emeryville, 94608, California, USA
Jill Cheng, Guoying K. Yu, Jianjun Yu & Vivien Chan - Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, 02115, Massachusetts, USA
Todd R. Golub - Howard Hughes Medical Institute, Chevy Chase, 20815, Maryland, USA
Todd R. Golub
Authors
- Jordi Barretina
- Giordano Caponigro
- Nicolas Stransky
- Kavitha Venkatesan
- Adam A. Margolin
- Sungjoon Kim
- Christopher J. Wilson
- Joseph Lehár
- Gregory V. Kryukov
- Dmitriy Sonkin
- Anupama Reddy
- Manway Liu
- Lauren Murray
- Michael F. Berger
- John E. Monahan
- Paula Morais
- Jodi Meltzer
- Adam Korejwa
- Judit Jané-Valbuena
- Felipa A. Mapa
- Joseph Thibault
- Eva Bric-Furlong
- Pichai Raman
- Aaron Shipway
- Ingo H. Engels
- Jill Cheng
- Guoying K. Yu
- Jianjun Yu
- Peter Aspesi
- Melanie de Silva
- Kalpana Jagtap
- Michael D. Jones
- Li Wang
- Charles Hatton
- Emanuele Palescandolo
- Supriya Gupta
- Scott Mahan
- Carrie Sougnez
- Robert C. Onofrio
- Ted Liefeld
- Laura MacConaill
- Wendy Winckler
- Michael Reich
- Nanxin Li
- Jill P. Mesirov
- Stacey B. Gabriel
- Gad Getz
- Kristin Ardlie
- Vivien Chan
- Vic E. Myer
- Barbara L. Weber
- Jeff Porter
- Markus Warmuth
- Peter Finan
- Jennifer L. Harris
- Matthew Meyerson
- Todd R. Golub
- Michael P. Morrissey
- William R. Sellers
- Robert Schlegel
- Levi A. Garraway
Contributions
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 toRobert 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.
Supplementary information
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)
Supplementary Tables
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). https://doi.org/10.1038/nature11003
- Received: 25 July 2011
- Accepted: 01 March 2012
- Published: 28 March 2012
- Issue Date: 29 March 2012
- DOI: https://doi.org/10.1038/nature11003