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

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

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

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Date

2012

Type de document

Articles

Périmètre

Publications

Langue

Anglais

Identifiants

doi: 10.1038/nature11005
issn: 0028-0836

Source

Serveur académique Lausannois

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Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1038/nature11005

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/22460902

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1476-4687

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_062794FBE8EB4

Collection

Serveur Académique Lausannois

Organisation

Université de Lausanne et CHUV

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info:eu-repo/semantics/openAccess , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer

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Carcinoma Cancers Malignancy (Cancer) Malignant tumors

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M.J. Garnett et al., « Systematic identification of genomic markers of drug sensitivity in cancer cells. », Serveur académique Lausannois, ID : 10.1038/nature11005

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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.

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

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