| |  Online-Ressource |
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| Verfasst von: | Tomska, Katarzyna [VerfasserIn]  |
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| | Kurilov, Roman [VerfasserIn] |
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| | Lee, Kwang Seok [VerfasserIn] |
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| | Hüllein, Jennifer [VerfasserIn] |
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| | Lukas, Marina [VerfasserIn] |
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| | Sellner, Leopold [VerfasserIn] |
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| | Walther, Tatjana [VerfasserIn] |
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| | Wagner, Lena [VerfasserIn] |
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| | Oleś, Małgorzata [VerfasserIn] |
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| | Brors, Benedikt [VerfasserIn] |
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| | Huber, Wolfgang [VerfasserIn] |
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| | Zenz, Thorsten [VerfasserIn] |
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| Titel: | Drug-based perturbation screen uncovers synergistic drug combinations in Burkitt lymphoma |
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| Verf.angabe: | K. Tomska, R. Kurilov, K.S. Lee, J. Hüllein, M. Lukas, L. Sellner, T. Walther, L. Wagner, M. Oleś, B. Brors, W. Huber & T. Zenz |
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| E-Jahr: | 2018 |
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| Jahr: | 13 August 2018 |
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| Umfang: | 12 S. |
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| Fussnoten: | Gesehen am 03.07.2019 |
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| Titel Quelle: | Enthalten in: Scientific reports |
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| Ort Quelle: | [London] : Macmillan Publishers Limited, part of Springer Nature, 2011 |
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| Jahr Quelle: | 2018 |
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| Band/Heft Quelle: | 8(2018) Artikel-Nummer 12046 |
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| ISSN Quelle: | 2045-2322 |
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| Abstract: | Burkitt lymphoma (BL) is a highly aggressive B-cell lymphoma associated with MYC translocation. Here, we describe drug response profiling of 42 blood cancer cell lines including 17 BL to 32 drugs targeting key cancer pathways and provide a systematic study of drug combinations in BL cell lines. Based on drug response, we identified cell line specific sensitivities, i.e. to venetoclax driven by BCL2 overexpression and partitioned subsets of BL driven by response to kinase inhibitors. In the combination screen, including BET, BTK and PI3K inhibitors, we identified synergistic combinations of PI3K and BTK inhibition with drugs targeting Akt, mTOR, BET and doxorubicin. A detailed comparison of PI3K and BTKi combinations identified subtle differences, in line with convergent pathway activity. Most synergistic combinations were identified for the BET inhibitor OTX015, which showed synergistic effects for 41% of combinations including inhibitors of PI3K/AKT/mTOR signalling. The strongest synergy was observed for the combination of the CDK 2/7/9 inhibitor SNS032 and OTX015. Our data provide a landscape of drug combination effects in BL and suggest that targeting CDK and BET could provide a novel vulnerability of BL. |
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| DOI: | doi:10.1038/s41598-018-30509-3 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1038/s41598-018-30509-3 |
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| | Volltext: https://www.nature.com/articles/s41598-018-30509-3 |
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| | DOI: https://doi.org/10.1038/s41598-018-30509-3 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1668453584 |
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| Verknüpfungen: | → Zeitschrift |
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Drug-based perturbation screen uncovers synergistic drug combinations in Burkitt lymphoma / Tomska, Katarzyna [VerfasserIn]; 13 August 2018 (Online-Ressource)
