Systematic identification of genomic markers of drug sensitivity in cancer cells.

Garnett, M.J.; Edelman, E.J.; Heidorn, S.J.; Greenman, C.D.; Dastur, A.; Lau, K.W.; Greninger, P.; Thompson, I.R.; Luo, X.; Soares, J.; Liu, Q.; Iorio, F.; Surdez, D.; Chen, L.; Milano, R.J.; Bignell, G.R.; Tam, A.T.; Davies, H.; Stevenson, J.A.; Barthorpe, S.; Lutz, S.R.; Kogera, F.; Lawrence, K.; McLaren-Douglas, A.; Mitropoulos, X.; Mironenko, T.; Thi, H.; Richardson, L.; Zhou, W.; Jewitt, F.; Zhang, T.; O'Brien, P.; Boisvert, J.L.; Price, S.; Hur, W.; Yang, W.; Deng, X.; Butler, A.; Choi, H.G.; Chang, J.W.; Baselga, J.; Stamenkovic, I.; Engelman, J.A.; Sharma, S.V.; Delattre, O.; Saez-Rodriguez, J.; Gray, N.S.; Settleman, J.; Futreal, P.A.; Haber, D.A.; Stratton, M.R.; Ramaswamy, S.; McDermott, U.; Benes, C.H.

doi:10.1038/nature11005

Systematic identification of genomic markers of drug sensitivity in cancer cells.

Details

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Serval ID

serval:BIB_062794FBE8EB

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

Systematic identification of genomic markers of drug sensitivity in cancer cells.

Journal

Nature

Author(s)

Garnett M.J., Edelman E.J., Heidorn S.J., Greenman C.D., Dastur A., Lau K.W., Greninger P., Thompson I.R., Luo X., Soares J., Liu Q., Iorio F., Surdez D., Chen L., Milano R.J., Bignell G.R., Tam A.T., Davies H., Stevenson J.A., Barthorpe S., Lutz S.R., Kogera F., Lawrence K., McLaren-Douglas A., Mitropoulos X., Mironenko T., Thi H., Richardson L., Zhou W., Jewitt F., Zhang T., O'Brien P., Boisvert J.L., Price S., Hur W., Yang W., Deng X., Butler A., Choi H.G., Chang J.W., Baselga J., Stamenkovic I., Engelman J.A., Sharma S.V., Delattre O., Saez-Rodriguez J., Gray N.S., Settleman J., Futreal P.A., Haber D.A., Stratton M.R., Ramaswamy S., McDermott U., Benes C.H.

ISSN

1476-4687 (Electronic)

ISSN-L

0028-0836

Publication state

Published

Issued date

2012

Peer-reviewed

Oui

Volume

483

Number

7391

Pages

570-575

Language

english

Notes

Publication types: Journal Article

Abstract

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

URN

urn:nbn:ch:serval-BIB_062794FBE8EB4

OAI-PMH

oai:serval.unil.ch:BIB_062794FBE8EB

DOI

10.1038/nature11005

Pubmed

22460902

Web of science

000302006100033

Create date

05/05/2012 15:52