دورية أكاديمية
Druggable growth dependencies and tumor evolution analysis in patient-derived organoids of neuroendocrine neoplasms from multiple body sites.
| العنوان: | Druggable growth dependencies and tumor evolution analysis in patient-derived organoids of neuroendocrine neoplasms from multiple body sites. |
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| المؤلفون: | Dayton TL; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands. Electronic address: talya.dayton@embl.es., Alcala N; Rare Cancers Genomics Team (RCG), Genomic Epidemiology Branch (GEM), International Agency for Research on Cancer/World Health Organisation (IARC/WHO), 69007 Lyon, France., Moonen L; Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Centre, 6229 ER Maastricht, the Netherlands., den Hartigh L; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands., Geurts V; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands., Mangiante L; Rare Cancers Genomics Team (RCG), Genomic Epidemiology Branch (GEM), International Agency for Research on Cancer/World Health Organisation (IARC/WHO), 69007 Lyon, France., Lap L; Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Centre, 6229 ER Maastricht, the Netherlands., Dost AFM; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands., Beumer J; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands., Levy S; Department of Medical Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands., van Leeuwaarde RS; Department of Endocrine Oncology, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands., Hackeng WM; Department of Pathology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands., Samsom K; Department of Pathology, Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands., Voegele C; Rare Cancers Genomics Team (RCG), Genomic Epidemiology Branch (GEM), International Agency for Research on Cancer/World Health Organisation (IARC/WHO), 69007 Lyon, France., Sexton-Oates A; Rare Cancers Genomics Team (RCG), Genomic Epidemiology Branch (GEM), International Agency for Research on Cancer/World Health Organisation (IARC/WHO), 69007 Lyon, France., Begthel H; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands., Korving J; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands., Hillen L; Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Centre, 6229 ER Maastricht, the Netherlands., Brosens LAA; Department of Pathology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands., Lantuejoul S; Department of Biopathology, Pathology Research Platform- Synergie Lyon Cancer- CRCL, Centre Léon Bérard Unicancer, 69008 Lyon, France; Université Grenoble Alpes, Grenoble, France., Jaksani S; Hubrecht Organoid Technology, Utrecht 3584 CM, the Netherlands., Kok NFM; Department of Surgery, Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands., Hartemink KJ; Department of Surgery, Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands., Klomp HM; Department of Surgery, Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands., Borel Rinkes IHM; Department of Endocrine Surgical Oncology, University Medical Center Utrecht, Utrecht 3508 GA, the Netherlands., Dingemans AM; Department of Pulmonary Diseases, GROW School for Oncology and and Reproduction, Maastricht University Medical Centre, Maastricht, the Netherlands; Department of Pulmonary Medicine, Erasmus MC Cancer Institute, University Medical Center, Rotterdam 3015 GD, the Netherlands., Valk GD; Department of Endocrine Oncology, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands., Vriens MR; Department of Endocrine Surgical Oncology, University Medical Center Utrecht, Utrecht 3508 GA, the Netherlands., Buikhuisen W; Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands., van den Berg J; Department of Pathology, Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands., Tesselaar M; Department of Medical Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands., Derks J; Department of Pulmonary Diseases, GROW School for Oncology and and Reproduction, Maastricht University Medical Centre, Maastricht, the Netherlands., Speel EJ; Department of Pathology, GROW School for Oncology and Reproduction, Maastricht University Medical Centre, 6229 ER Maastricht, the Netherlands., Foll M; Rare Cancers Genomics Team (RCG), Genomic Epidemiology Branch (GEM), International Agency for Research on Cancer/World Health Organisation (IARC/WHO), 69007 Lyon, France., Fernández-Cuesta L; Rare Cancers Genomics Team (RCG), Genomic Epidemiology Branch (GEM), International Agency for Research on Cancer/World Health Organisation (IARC/WHO), 69007 Lyon, France. Electronic address: fernandezcuestal@iarc.who.int., Clevers H; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, 3584 CT Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, 3584 CT Utrecht, the Netherlands. Electronic address: h.clevers@hubrecht.eu. |
| المصدر: | Cancer cell [Cancer Cell] 2023 Dec 11; Vol. 41 (12), pp. 2083-2099.e9. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101130617 Publication Model: Print Cited Medium: Internet ISSN: 1878-3686 (Electronic) Linking ISSN: 15356108 NLM ISO Abbreviation: Cancer Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press, c2002- |
| مواضيع طبية MeSH: | Neuroendocrine Tumors*/drug therapy , Neuroendocrine Tumors*/genetics , Neuroendocrine Tumors*/metabolism , Carcinoma, Neuroendocrine*/drug therapy , Carcinoma, Neuroendocrine*/genetics , Carcinoma, Neuroendocrine*/metabolism , Lung Neoplasms*/drug therapy , Lung Neoplasms*/genetics , Pancreatic Neoplasms*/pathology, Humans |
| مستخلص: | 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. Competing Interests: Declaration of interests Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization. H.C.’s full disclosure is given at https://www.uu.nl/staff/JCClevers/. H.C. is inventor of several patents related to organoid technology, cofounder of Xilis Inc. and currently an employee of Roche, Basel. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: Cancer Cell. 2023 Dec 11;41(12):2014-2016. (PMID: 38086333) |
| معلومات مُعتمدة: | 001 International WHO_ World Health Organization |
| فهرسة مساهمة: | Keywords: biomarker; cancer; cell neuroendocrine carcinoma; genomics; growth factor depenencies; intra-tumor heterogeneity; lung cancer; neuroendocrine tumorlarge; organoids; tumor evolution |
| تواريخ الأحداث: | Date Created: 20231212 Date Completed: 20231216 Latest Revision: 20240312 |
| رمز التحديث: | 20240313 |
| DOI: | 10.1016/j.ccell.2023.11.007 |
| PMID: | 38086335 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1878-3686 |
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| DOI: | 10.1016/j.ccell.2023.11.007 |