Systematic identification of genomic markers of drug sensitivity in cancer cells
| Autor: | Xeni Mitropoulos, Jae Won Chang, Daniel A. Haber, Jeffrey Settleman, Wanjuan Yang, I. Richard Thompson, Julio Saez-Rodriguez, Nathanael S. Gray, Olivier Delattre, Jeffrey A. Engelman, Qingsong Liu, Sonja J. Heidorn, José Baselga, Michael R. Stratton, Karl P. Lawrence, Helen Davies, Stephen R. Lutz, Li Chen, Helen Thi, Graham R. Bignell, Randy J. Milano, Anne McLaren-Douglas, Anahita Dastur, Sridhar Ramaswamy, Sreenath V. Sharma, Jesse A. Stevenson, Patricia Greninger, Jessica L. Boisvert, King Wai Lau, Xi Luo, Tatiana Mironenko, Xianming Deng, Christopher Greenman, Fiona Kogera, P. Andrew Futreal, Tinghu Zhang, Patrick O’Brien, Syd Barthorpe, F Jewitt, Ultan McDermott, Hwan Geun Choi, Mathew J. Garnett, Ivan Stamenkovic, Francesco Iorio, Wooyoung Hur, Stacey Price, Jorge Soares, Laura Richardson, Wenjun Zhou, Cyril H. Benes, Ah Ting Tam, Adam Butler, Elena J. Edelman, Didier Surdez |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Genetic Markers
Indoles Oncogene Proteins Fusion Cell Survival Sarcoma Ewing Poly(ADP-ribose) Polymerase Inhibitors Biology Bioinformatics Poly (ADP-Ribose) Polymerase Inhibitor Piperazines Article 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Neoplasms Humans Biomarker discovery 030304 developmental biology 0303 health sciences Multidisciplinary Genome Human Proto-Oncogene Protein c-fli-1 Genomics Oncogene Addiction Human genetics 3. Good health Gene Expression Regulation Neoplastic Drug Resistance Neoplasm Pharmacogenetics 030220 oncology & carcinogenesis Pharmacogenomics Cancer cell Cancer research Phthalazines Human genome Drug Screening Assays Antitumor RNA-Binding Protein EWS Genes Neoplasm |
| Zdroj: | Nature Nature, vol. 483, no. 7391, pp. 570-575 |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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