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| Verfasst von: | Wong, Nelson K. Y. [VerfasserIn]  |
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| | Llaurado Fernandez, Marta [VerfasserIn] |
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| | Kommoss, Felix [VerfasserIn] |
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| | Praveen Kumar, Pooja [VerfasserIn] |
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| | Kim, Hannah [VerfasserIn] |
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| | Liu, Jiahui [VerfasserIn] |
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| | Zhang, Guihua [VerfasserIn] |
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| | Coatham, Mackenzie [VerfasserIn] |
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| | Lin, Yen-Yi [VerfasserIn] |
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| | Haegert, Anne M. [VerfasserIn] |
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| | Volik, Stanislav [VerfasserIn] |
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| | Le Bihan, Stephane [VerfasserIn] |
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| | Collins, Colin C. [VerfasserIn] |
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| | Fu, Yangxin [VerfasserIn] |
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| | Postovit, Lynne M. [VerfasserIn] |
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| | Deimling, Andreas von [VerfasserIn] |
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| | Wu, Rebecca [VerfasserIn] |
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| | Xue, Hui [VerfasserIn] |
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| | Wang, Yuzhuo [VerfasserIn] |
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| | Köbel, Martin [VerfasserIn] |
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| | Carey, Mark S. [VerfasserIn] |
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| | Lee, Cheng-Han [VerfasserIn] |
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| Titel: | Establishment and validation of preclinical models of SMARCA4-inactivated and ARID1A/ARID1B co-inactivated dedifferentiated endometrial carcinoma |
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| Verf.angabe: | Nelson K. Y. Wong, Marta Llaurado Fernandez, Felix K. F. Kommoss, Pooja Praveen Kumar, Hannah Kim, Jiahui Liu, Guihua Zhang, Mackenzie Coatham, Yen-Yi Lin, Anne M. Haegert, Stanislav Volik, Stephane Le Bihan, Colin C. Collins, Yangxin Fu, Lynne M. Postovit, Andreas von Deimling, Rebecca Wu, Hui Xue, Yuzhuo Wang, Martin Köbel, Mark S. Carey, Cheng-Han Lee |
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| E-Jahr: | 2023 |
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| Jahr: | 7 August 2023 |
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| Umfang: | 11 S. |
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| Fussnoten: | Gesehen am 06.02.2024 |
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| Titel Quelle: | Enthalten in: Gynecologic oncology |
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| Ort Quelle: | Orlando, Fla. : Academic Press, 1972 |
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| Jahr Quelle: | 2023 |
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| Band/Heft Quelle: | 176(2023), Seite 162-172 |
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| ISSN Quelle: | 1095-6859 |
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| Abstract: | Objective - Dedifferentiated endometrial cancer (DDEC) is an uncommon and clinically highly aggressive subtype of endometrial cancer characterized by genomic inactivation of SWItch/Sucrose Non-Fermentable (SWI/SNF) complex protein. It responds poorly to conventional systemic treatment and its rapidly progressive clinical course limits the therapeutic windows to trial additional lines of therapies. This underscores a pressing need for biologically accurate preclinical tumor models to accelerate therapeutic development. - Methods - DDEC tumor from surgical samples were implanted into immunocompromised mice for patient-derived xenograft (PDX) and cell line development. The histologic, immunophenotypic, genetic and epigenetic features of the patient tumors and the established PDX models were characterized. The SMARCA4-deficienct DDEC model was evaluated for its sensitivity toward a KDM6A/B inhibitor (GSK-J4) that was previously reported to be effective therapy for other SMARCA4-deficient cancer types. - Results - All three DDEC models exhibited rapid growth in vitro and in vivo, with two PDX models showing spontaneous development of metastases in vivo. The PDX tumors maintained the same undifferentiated histology and immunophenotype, and exhibited identical genomic and methylation profiles as seen in the respective parental tumors, including a mismatch repair (MMR)-deficient DDEC with genomic inactivation of SMARCA4, and two MMR-deficient DDECs with genomic inactivation of both ARID1A and ARID1B. Although the SMARCA4-deficient cell line showed low micromolecular sensitivity to GSK-J4, no significant tumor growth inhibition was observed in the corresponding PDX model. - Conclusions - These established patient tumor-derived models accurately depict DDEC and represent valuable preclinical tools to gain therapeutic insights into this aggressive tumor type. |
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| DOI: | doi:10.1016/j.ygyno.2023.07.016 |
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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.
kostenfrei: Volltext: https://doi.org/10.1016/j.ygyno.2023.07.016 |
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| | kostenfrei: Volltext: https://www.sciencedirect.com/science/article/pii/S0090825823014178 |
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| | DOI: https://doi.org/10.1016/j.ygyno.2023.07.016 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Dedifferentiated cancer |
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| | SWI/SNF |
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| | Undifferentiated cancer |
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| | Xenograft |
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| K10plus-PPN: | 1880061279 |
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| Verknüpfungen: | → Zeitschrift |
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Establishment and validation of preclinical models of SMARCA4-inactivated and ARID1A/ARID1B co-inactivated dedifferentiated endometrial carcinoma / Wong, Nelson K. Y. [VerfasserIn]; 7 August 2023 (Online-Ressource)
