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

Details

Serval ID
serval:BIB_062794FBE8EB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
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.
Pubmed
Web of science
Create date
05/05/2012 15:52
Last modification date
20/08/2019 12:28
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