| |  Online-Ressource |
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| Verfasst von: | Schneeweiss-Gleixner, Mathias [VerfasserIn]  |
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| | Filik, Yüksel [VerfasserIn] |
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| | Stefanzl, Gabriele [VerfasserIn] |
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| | Berger, Daniela [VerfasserIn] |
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| | Sadovnik, Irina [VerfasserIn] |
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| | Bauer, Karin [VerfasserIn] |
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| | Smiljkovic, Dubravka [VerfasserIn] |
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| | Eisenwort, Gregor [VerfasserIn] |
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| | Witzeneder, Nadine [VerfasserIn] |
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| | Greiner, Georg [VerfasserIn] |
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| | Hoermann, Gregor [VerfasserIn] |
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| | Schiefer, Ana-Iris [VerfasserIn] |
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| | Schwaab, Juliana [VerfasserIn] |
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| | Jawhar, Mohamad [VerfasserIn] |
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| | Reiter, Andreas [VerfasserIn] |
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| | Sperr, Wolfgang R. [VerfasserIn] |
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| | Arock, Michel [VerfasserIn] |
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| | Valent, Peter [VerfasserIn] |
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| | Gleixner, Karoline V. [VerfasserIn] |
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| Titel: | CDK4/CDK6 inhibitors synergize with Midostaurin, Avapritinib, and Nintedanib in inducing growth inhibition in KIT D816V+ neoplastic mast cells |
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| Verf.angabe: | Mathias Schneeweiss-Gleixner, Yüksel Filik, Gabriele Stefanzl, Daniela Berger, Irina Sadovnik, Karin Bauer, Dubravka Smiljkovic, Gregor Eisenwort, Nadine Witzeneder, Georg Greiner, Gregor Hoermann, Ana-Iris Schiefer, Juliana Schwaab, Mohamad Jawhar, Andreas Reiter, Wolfgang R. Sperr, Michel Arock, Peter Valent and Karoline V. Gleixner |
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| E-Jahr: | 2022 |
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| Jahr: | 23 June 2022 |
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| Umfang: | 29 S. |
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| Fussnoten: | Im Titel ist "+" hochgestellt ; Gesehen am 23.08.2022 |
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| Titel Quelle: | Enthalten in: Cancers |
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| Ort Quelle: | Basel : MDPI, 2009 |
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| Jahr Quelle: | 2022 |
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| Band/Heft Quelle: | 14(2022), 13, Artikel-ID 3070, Seite 1-29 |
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| ISSN Quelle: | 2072-6694 |
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| Abstract: | In most patients with advanced systemic mastocytosis (AdvSM), neoplastic mast cells (MC) express KIT D816V. However, despite their disease-modifying potential, KIT D816V-targeting drugs, including midostaurin and avapritinib, may not produce long-term remissions in all patients. Cyclin-dependent kinase (CDK) 4 and CDK6 are promising targets in oncology. We found that shRNA-mediated knockdown of CDK4 and CDK6 results in growth arrest in the KIT D816V+ MC line HMC-1.2. The CDK4/CDK6 inhibitors palbociclib, ribociclib, and abemaciclib suppressed the proliferation in primary neoplastic MC as well as in all HMC-1 and ROSA cell subclones that were examined. Abemaciclib was also found to block growth in the drug-resistant MC line MCPV-1, whereas no effects were seen with palbociclib and ribociclib. Anti-proliferative drug effects on MC were accompanied by cell cycle arrest. Furthermore, CDK4/CDK6 inhibitors were found to synergize with the KIT-targeting drugs midostaurin, avapritinib, and nintedanib in inducing growth inhibition and apoptosis in neoplastic MCs. Finally, we found that CDK4/CDK6 inhibitors induce apoptosis in CD34+/CD38- stem cells in AdvSM. Together, CDK4/CDK6 inhibition is a potent approach to suppress the growth of neoplastic cells in AdvSM. Whether CDK4/CDK6 inhibitors can improve clinical outcomes in patients with AdvSM remains to be determined in clinical trials. |
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| DOI: | doi:10.3390/cancers14133070 |
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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: https://doi.org/10.3390/cancers14133070 |
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| | DOI: https://doi.org/10.3390/cancers14133070 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | abemaciclib |
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| | avapritinib |
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| | CDK4/CDK6 |
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| | drug-combinations |
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| | KIT D816V |
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| | midostaurin |
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| | palbociclib |
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| | ribociclib |
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| | systemic mastocytosis |
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| | targeted therapy |
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| K10plus-PPN: | 1814978003 |
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| Verknüpfungen: | → Zeitschrift |
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CDK4/CDK6 inhibitors synergize with Midostaurin, Avapritinib, and Nintedanib in inducing growth inhibition in KIT D816V+ neoplastic mast cells / Schneeweiss-Gleixner, Mathias [VerfasserIn]; 23 June 2022 (Online-Ressource)
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