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Systematic identification of genomic markers of drug sensitivity in cancer cells
Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. To uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred ca...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2012
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349233/ https://www.ncbi.nlm.nih.gov/pubmed/22460902 http://dx.doi.org/10.1038/nature11005 |
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| author | Garnett, Mathew J. Edelman, Elena J. Heidorn, Sonja J. Greenman, Chris D. Dastur, Anahita Lau, King Wai Greninger, Patricia Thompson, I. Richard Luo, Xi Soares, Jorge Liu, Qingsong Iorio, Francesco Surdez, Didier Chen, Li Milano, Randy J. Bignell, Graham R. Tam, Ah T. Davies, Helen Stevenson, Jesse A. Barthorpe, Syd Lutz, Stephen R. Kogera, Fiona Lawrence, Karl McLaren-Douglas, Anne Mitropoulos, Xeni Mironenko, Tatiana Thi, Helen Richardson, Laura Zhou, Wenjun Jewitt, Frances Zhang, Tinghu O’Brien, Patrick Boisvert, Jessica L. Price, Stacey Hur, Wooyoung Yang, Wanjuan Deng, Xianming Butler, Adam Choi, Hwan Geun Chang, Jae Won Baselga, Jose Stamenkovic, Ivan Engelman, Jeffrey A. Sharma, Sreenath V. Delattre, Olivier Saez-Rodriguez, Julio Gray, Nathanael S. Settleman, Jeffrey Futreal, P. Andrew Haber, Daniel A. Stratton, Michael R. Ramaswamy, Sridhar McDermott, Ultan Benes, Cyril H. |
| author_facet | Garnett, Mathew J. Edelman, Elena J. Heidorn, Sonja J. Greenman, Chris D. Dastur, Anahita Lau, King Wai Greninger, Patricia Thompson, I. Richard Luo, Xi Soares, Jorge Liu, Qingsong Iorio, Francesco Surdez, Didier Chen, Li Milano, Randy J. Bignell, Graham R. Tam, Ah T. Davies, Helen Stevenson, Jesse A. Barthorpe, Syd Lutz, Stephen R. Kogera, Fiona Lawrence, Karl McLaren-Douglas, Anne Mitropoulos, Xeni Mironenko, Tatiana Thi, Helen Richardson, Laura Zhou, Wenjun Jewitt, Frances Zhang, Tinghu O’Brien, Patrick Boisvert, Jessica L. Price, Stacey Hur, Wooyoung Yang, Wanjuan Deng, Xianming Butler, Adam Choi, Hwan Geun Chang, Jae Won Baselga, Jose Stamenkovic, Ivan Engelman, Jeffrey A. Sharma, Sreenath V. Delattre, Olivier Saez-Rodriguez, Julio Gray, Nathanael S. Settleman, Jeffrey Futreal, P. Andrew Haber, Daniel A. Stratton, Michael R. Ramaswamy, Sridhar McDermott, Ultan Benes, Cyril H. |
| author_sort | Garnett, Mathew J. |
| collection | PubMed |
| description | Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. 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 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 harboring the EWS-FLI1 gene translocation to 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. |
| format | Online Article Text |
| id | pubmed-3349233 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2012 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-33492332012-09-29 Systematic identification of genomic markers of drug sensitivity in cancer cells Garnett, Mathew J. Edelman, Elena J. Heidorn, Sonja J. Greenman, Chris D. Dastur, Anahita Lau, King Wai Greninger, Patricia Thompson, I. Richard Luo, Xi Soares, Jorge Liu, Qingsong Iorio, Francesco Surdez, Didier Chen, Li Milano, Randy J. Bignell, Graham R. Tam, Ah T. Davies, Helen Stevenson, Jesse A. Barthorpe, Syd Lutz, Stephen R. Kogera, Fiona Lawrence, Karl McLaren-Douglas, Anne Mitropoulos, Xeni Mironenko, Tatiana Thi, Helen Richardson, Laura Zhou, Wenjun Jewitt, Frances Zhang, Tinghu O’Brien, Patrick Boisvert, Jessica L. Price, Stacey Hur, Wooyoung Yang, Wanjuan Deng, Xianming Butler, Adam Choi, Hwan Geun Chang, Jae Won Baselga, Jose Stamenkovic, Ivan Engelman, Jeffrey A. Sharma, Sreenath V. Delattre, Olivier Saez-Rodriguez, Julio Gray, Nathanael S. Settleman, Jeffrey Futreal, P. Andrew Haber, Daniel A. Stratton, Michael R. Ramaswamy, Sridhar McDermott, Ultan Benes, Cyril H. Nature Article Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. 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 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 harboring the EWS-FLI1 gene translocation to 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. 2012-03-28 /pmc/articles/PMC3349233/ /pubmed/22460902 http://dx.doi.org/10.1038/nature11005 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
| spellingShingle | Article Garnett, Mathew J. Edelman, Elena J. Heidorn, Sonja J. Greenman, Chris D. Dastur, Anahita Lau, King Wai Greninger, Patricia Thompson, I. Richard Luo, Xi Soares, Jorge Liu, Qingsong Iorio, Francesco Surdez, Didier Chen, Li Milano, Randy J. Bignell, Graham R. Tam, Ah T. Davies, Helen Stevenson, Jesse A. Barthorpe, Syd Lutz, Stephen R. Kogera, Fiona Lawrence, Karl McLaren-Douglas, Anne Mitropoulos, Xeni Mironenko, Tatiana Thi, Helen Richardson, Laura Zhou, Wenjun Jewitt, Frances Zhang, Tinghu O’Brien, Patrick Boisvert, Jessica L. Price, Stacey Hur, Wooyoung Yang, Wanjuan Deng, Xianming Butler, Adam Choi, Hwan Geun Chang, Jae Won Baselga, Jose Stamenkovic, Ivan Engelman, Jeffrey A. Sharma, Sreenath V. Delattre, Olivier Saez-Rodriguez, Julio Gray, Nathanael S. Settleman, Jeffrey Futreal, P. Andrew Haber, Daniel A. Stratton, Michael R. Ramaswamy, Sridhar McDermott, Ultan Benes, Cyril H. Systematic identification of genomic markers of drug sensitivity in cancer cells |
| title | Systematic identification of genomic markers of drug sensitivity in cancer cells |
| title_full | Systematic identification of genomic markers of drug sensitivity in cancer cells |
| title_fullStr | Systematic identification of genomic markers of drug sensitivity in cancer cells |
| title_full_unstemmed | Systematic identification of genomic markers of drug sensitivity in cancer cells |
| title_short | Systematic identification of genomic markers of drug sensitivity in cancer cells |
| title_sort | systematic identification of genomic markers of drug sensitivity in cancer cells |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349233/ https://www.ncbi.nlm.nih.gov/pubmed/22460902 http://dx.doi.org/10.1038/nature11005 |
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