Registered report: Systematic identification of genomic markers of drug sensitivity in cancer cells
The Reproducibility Project: Cancer Biology seeks to address growing concerns about the reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 201...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/13620 |
| _version_ | 1818019220415315968 |
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| author | John P Vanden Heuvel Jessica Bullenkamp Reproducibility Project: Cancer Biology |
| author_facet | John P Vanden Heuvel Jessica Bullenkamp Reproducibility Project: Cancer Biology |
| author_sort | John P Vanden Heuvel |
| collection | DOAJ |
| description | The Reproducibility Project: Cancer Biology seeks to address growing concerns about the reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from “Systematic identification of genomic markers of drug sensitivity in cancer cells” by Garnett and colleagues, published in Nature in 2012 (Garnett et al., 2012). The experiments to be replicated are those reported in Figures 4C, 4E, 4F, and Supplemental Figures 16 and 20. Garnett and colleagues performed a high throughput screen assessing the effect of 130 drugs on 639 cancer-derived cell lines in order to identify novel interactions for possible therapeutic approaches. They then tested this approach by exploring in more detail a novel interaction they identified in which Ewing’s sarcoma cell lines showed an increased sensitivity to PARP inhibitors (Figure 4C). Mesenchymal progenitor cells (MPCs) transformed with the signature EWS-FLI1 translocation, the hallmark of Ewing’s sarcoma family tumors, exhibited increased sensitivity to the PARP inhibitor olaparib as compared to MPCs transformed with a different translocation (Figure 4E). Knockdown mediated by siRNA of EWS-FLI1 abrogated this sensitivity to olaparib (Figure 4F). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife. |
| first_indexed | 2024-04-14T07:49:25Z |
| format | Article |
| id | doaj.art-fa89872cdd1d4769b8078f759a5c7cb8 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:49:25Z |
| publishDate | 2016-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-fa89872cdd1d4769b8078f759a5c7cb82022-12-22T02:05:15ZengeLife Sciences Publications LtdeLife2050-084X2016-06-01510.7554/eLife.13620Registered report: Systematic identification of genomic markers of drug sensitivity in cancer cellsJohn P Vanden Heuvel0Jessica Bullenkamp1Reproducibility Project: Cancer BiologyIndigo Biosciences, State College, United States; Veterinary and Biomedical Sciences, Penn State University, University Park, PA, United StatesKing's College London, London, United KingdomThe Reproducibility Project: Cancer Biology seeks to address growing concerns about the reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from “Systematic identification of genomic markers of drug sensitivity in cancer cells” by Garnett and colleagues, published in Nature in 2012 (Garnett et al., 2012). The experiments to be replicated are those reported in Figures 4C, 4E, 4F, and Supplemental Figures 16 and 20. Garnett and colleagues performed a high throughput screen assessing the effect of 130 drugs on 639 cancer-derived cell lines in order to identify novel interactions for possible therapeutic approaches. They then tested this approach by exploring in more detail a novel interaction they identified in which Ewing’s sarcoma cell lines showed an increased sensitivity to PARP inhibitors (Figure 4C). Mesenchymal progenitor cells (MPCs) transformed with the signature EWS-FLI1 translocation, the hallmark of Ewing’s sarcoma family tumors, exhibited increased sensitivity to the PARP inhibitor olaparib as compared to MPCs transformed with a different translocation (Figure 4E). Knockdown mediated by siRNA of EWS-FLI1 abrogated this sensitivity to olaparib (Figure 4F). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife.https://elifesciences.org/articles/13620Reproducibility Project: Cancer BiologymethodologyEwing's sarcomapoly(ADP-ribose) polymerasePARPmesenchymal progenitor cells |
| spellingShingle | John P Vanden Heuvel Jessica Bullenkamp Reproducibility Project: Cancer Biology Registered report: Systematic identification of genomic markers of drug sensitivity in cancer cells eLife Reproducibility Project: Cancer Biology methodology Ewing's sarcoma poly(ADP-ribose) polymerase PARP mesenchymal progenitor cells |
| title | Registered report: Systematic identification of genomic markers of drug sensitivity in cancer cells |
| title_full | Registered report: Systematic identification of genomic markers of drug sensitivity in cancer cells |
| title_fullStr | Registered report: Systematic identification of genomic markers of drug sensitivity in cancer cells |
| title_full_unstemmed | Registered report: Systematic identification of genomic markers of drug sensitivity in cancer cells |
| title_short | Registered report: Systematic identification of genomic markers of drug sensitivity in cancer cells |
| title_sort | registered report systematic identification of genomic markers of drug sensitivity in cancer cells |
| topic | Reproducibility Project: Cancer Biology methodology Ewing's sarcoma poly(ADP-ribose) polymerase PARP mesenchymal progenitor cells |
| url | https://elifesciences.org/articles/13620 |
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