التفاصيل البيبلوغرافية
| العنوان: |
Druggable growth dependencies and tumor evolution analysis in patient-derived organoids of neuroendocrine neoplasms from multiple body sites |
| المؤلفون: |
Dayton, Talya L, Alcala, Nicolas, Moonen, Laura, den Hartigh, Lisanne, Geurts, Veerle, Mangiante, Lise, Lap, Lisa, Dost, Antonella F M, Beumer, Joep, Levy, Sonja, van Leeuwaarde, Rachel S, Hackeng, Wenzel M, Samsom, Kris, Voegele, Catherine, Sexton-Oates, Alexandra, Begthel, Harry, Korving, Jeroen, Hillen, Lisa, Brosens, Lodewijk A A, Lantuejoul, Sylvie, Jaksani, Sridevi, Kok, Niels F M, Hartemink, Koen J, Klomp, Houke M, Borel Rinkes, Inne H M, Dingemans, Anne-Marie, Valk, Gerlof D, Vriens, Menno R, Buikhuisen, Wieneke, van den Berg, José, Tesselaar, Margot, Derks, Jules, Speel, Ernst Jan, Foll, Matthieu, Fernández-Cuesta, Lynnette, Clevers, Hans |
| المساهمون: |
CMM Groep Maurice, Cancer, MS Endocriene Oncologie, Pathologie Groep Brosens, Pathologie Pathologen staf, MS CGO, Regenerative Medicine and Stem Cells, Heelkunde Opleiding, CMM, Hubrecht Institute with UMC |
| سنة النشر: |
2023 |
| مصطلحات موضوعية: |
biomarker, cancer, cell neuroendocrine carcinoma, genomics, growth factor depenencies, intra-tumor heterogeneity, lung cancer, neuroendocrine tumorlarge, organoids, tumor evolution, Oncology, Cancer Research |
| الوصف: |
Neuroendocrine neoplasms (NENs) comprise well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Treatment options for patients with NENs are limited, in part due to lack of accurate models. We establish patient-derived tumor organoids (PDTOs) from pulmonary NETs and derive PDTOs from an understudied subtype of NEC, large cell neuroendocrine carcinoma (LCNEC), arising from multiple body sites. PDTOs maintain the gene expression patterns, intra-tumoral heterogeneity, and evolutionary processes of parental tumors. Through hypothesis-driven drug sensitivity analyses, we identify ASCL1 as a potential biomarker for response of LCNEC to treatment with BCL-2 inhibitors. Additionally, we discover a dependency on EGF in pulmonary NET PDTOs. Consistent with these findings, we find that, in an independent cohort, approximately 50% of pulmonary NETs express EGFR. This study identifies an actionable vulnerability for a subset of pulmonary NETs, emphasizing the utility of these PDTO models. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| تدمد: |
1535-6108 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/450667 |
| الاتاحة: |
https://dspace.library.uu.nl/handle/1874/450667 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: |
edsbas.3D1AAD85 |
| قاعدة البيانات: |
BASE |
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