| Автор | Garnett, Mathew J. |
| Автор | Edelman, Elena J. |
| Автор | Heidorn, Sonja J. |
| Автор | Greenman, Chris D. |
| Автор | Dastur, Anahita |
| Автор | Lau, King Wai |
| Автор | Greninger, Patricia |
| Автор | Thompson, I. Richard |
| Автор | Luo, Xi |
| Автор | Soares, Jorge |
| Автор | Liu, Qingsong |
| Автор | Iorio, Francesco |
| Автор | Surdez, Didier |
| Автор | Chen, Li |
| Автор | Milano, Randy J. |
| Автор | Bignell, Graham R. |
| Автор | Tam, Ah T. |
| Автор | Davies, Helen |
| Автор | Stevenson, Jesse A. |
| Автор | Barthorpe, Syd |
| Автор | Lutz, Stephen R. |
| Автор | Kogera, Fiona |
| Автор | Lawrence, Karl |
| Автор | McLaren-Douglas, Anne |
| Автор | Mitropoulos, Xeni |
| Автор | Mironenko, Tatiana |
| Автор | Thi, Helen |
| Автор | Richardson, Laura |
| Автор | Zhou, Wenjun |
| Автор | Jewitt, Frances |
| Автор | Zhang, Tinghu |
| Автор | Oâ Brien, Patrick |
| Автор | Boisvert, Jessica L. |
| Автор | Price, Stacey |
| Автор | Hur, Wooyoung |
| Автор | Yang, Wanjuan |
| Автор | Deng, Xianming |
| Автор | Butler, Adam |
| Автор | Choi, Hwan Geun |
| Автор | Chang, Jae Won |
| Автор | Baselga, Jose |
| Автор | Stamenkovic, Ivan |
| Автор | Engelman, Jeffrey A. |
| Автор | Sharma, Sreenath V. |
| Автор | Delattre, Olivier |
| Автор | Saez-Rodriguez, Julio |
| Автор | Gray, Nathanael S. |
| Автор | Settleman, Jeffrey |
| Автор | Futreal, P. Andrew |
| Автор | Haber, Daniel A. |
| Автор | Stratton, Michael R. |
| Автор | Ramaswamy, Sridhar |
| Автор | McDermott, Ultan |
| Автор | Benes, Cyril H. |
| Дата выпуска | 2012 |
| dc.description | 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 linesâ which represent much of the tissue-type and genetic diversity of human cancersâ 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 Ewingâ 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. |
| Формат | application.pdf |
| Издатель | Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. |
| Копирайт | Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. |
| Название | Systematic identification of genomic markers of drug sensitivity in cancer cells |
| Тип | ARTICLE |
| DOI | 10.1038/nature11005 |
| Print ISSN | 0028-0836 |
| Журнал | Nature |
| Том | 483 |
| Первая страница | 570 |
| Последняя страница | 575 |
| Аффилиация | Garnett, Mathew J.; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Edelman, Elena J.; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | Heidorn, Sonja J.; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Greenman, Chris D.; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK; Department of Computing, University of East Anglia, Norwich NR4 7TJ, UK (C.D.G.); The Genome Analysis Centre, Norwich Research Park, Norwich NR4 7UH, UK (C.D.G.); Oncology Drug Discovery, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA (S.V.S.). |
| Аффилиация | Dastur, Anahita; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | Lau, King Wai; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Greninger, Patricia; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | Thompson, I. Richard; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Luo, Xi; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | Soares, Jorge; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Liu, Qingsong; Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston Massachusetts 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, Massachusetts 02115, USA |
| Аффилиация | Iorio, Francesco; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK; EMBL-EBI, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK |
| Аффилиация | Surdez, Didier; Laboratoire de génétique et biologie des cancers, Institut Curie, 75248 Paris, Cedex 05, France |
| Аффилиация | Chen, Li; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | Milano, Randy J.; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | Bignell, Graham R.; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Tam, Ah T.; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | Davies, Helen; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Stevenson, Jesse A.; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | Barthorpe, Syd; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Lutz, Stephen R.; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | Kogera, Fiona; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Lawrence, Karl; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | McLaren-Douglas, Anne; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Mitropoulos, Xeni; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | Mironenko, Tatiana; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Thi, Helen; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | Richardson, Laura; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Zhou, Wenjun; Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston Massachusetts 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, Massachusetts 02115, USA |
| Аффилиация | Jewitt, Frances; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Zhang, Tinghu; Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston Massachusetts 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, Massachusetts 02115, USA |
| Аффилиация | Oâ Brien, Patrick; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Boisvert, Jessica L.; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | Price, Stacey; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Hur, Wooyoung; Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston Massachusetts 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, Massachusetts 02115, USA |
| Аффилиация | Yang, Wanjuan; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Deng, Xianming; Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston Massachusetts 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, Massachusetts 02115, USA |
| Аффилиация | Butler, Adam; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Choi, Hwan Geun; Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston Massachusetts 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, Massachusetts 02115, USA |
| Аффилиация | Chang, Jae Won; Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston Massachusetts 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, Massachusetts 02115, USA |
| Аффилиация | Baselga, Jose; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | Stamenkovic, Ivan; Division of Experimental Pathology, Institute of Pathology, Centre Hospitalier Universitaire Vaudois (CHUV), 1005 Lausanne, Switzerland |
| Аффилиация | Engelman, Jeffrey A.; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | Sharma, Sreenath V.; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA; Department of Computing, University of East Anglia, Norwich NR4 7TJ, UK (C.D.G.); The Genome Analysis Centre, Norwich Research Park, Norwich NR4 7UH, UK (C.D.G.); Oncology Drug Discovery, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA (S.V.S.). |
| Аффилиация | Delattre, Olivier; Laboratoire de génétique et biologie des cancers, Institut Curie, 75248 Paris, Cedex 05, France |
| Аффилиация | Saez-Rodriguez, Julio; EMBL-EBI, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK |
| Аффилиация | Gray, Nathanael S.; Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston Massachusetts 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Boston, Massachusetts 02115, USA |
| Аффилиация | Settleman, Jeffrey; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | Futreal, P. Andrew; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Haber, Daniel A.; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA; Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA |
| Аффилиация | Stratton, Michael R.; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Ramaswamy, Sridhar; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Аффилиация | McDermott, Ultan; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK |
| Аффилиация | Benes, Cyril H.; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA |
| Выпуск | 7391 |
