Patient derived tumoroids of high grade neuroendocrine neoplasms for more personalized therapies.
Journal
NPJ precision oncology
ISSN: 2397-768X
Titre abrégé: NPJ Precis Oncol
Pays: England
ID NLM: 101708166
Informations de publication
Date de publication:
01 Mar 2024
01 Mar 2024
Historique:
received:
13
06
2023
accepted:
15
02
2024
medline:
2
3
2024
pubmed:
2
3
2024
entrez:
1
3
2024
Statut:
epublish
Résumé
There are no therapeutic predictive biomarkers or representative preclinical models for high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), a highly aggressive, fatal, and heterogeneous malignancy. We established patient-derived (PD) tumoroids from biobanked tissue samples of advanced high-grade GEP-NEN patients and applied this model for targeted rapid ex vivo pharmacotyping, next-generation sequencing, and perturbational profiling. We used tissue-matched PD tumoroids to profile individual patients, compared ex vivo drug response to patients' clinical response to chemotherapy, and investigated treatment-induced adaptive stress responses.PD tumoroids recapitulated biological key features of high-grade GEP-NEN and mimicked clinical response to cisplatin and temozolomide ex vivo. When we investigated treatment-induced adaptive stress responses in PD tumoroids in silico, we discovered and functionally validated Lysine demethylase 5 A and interferon-beta, which act synergistically in combination with cisplatin. Since ex vivo drug response in PD tumoroids matched clinical patient responses to standard-of-care chemotherapeutics for GEP-NEN, our rapid and functional precision oncology approach could expand personalized therapeutic options for patients with advanced high-grade GEP-NEN.
Identifiants
pubmed: 38429350
doi: 10.1038/s41698-024-00549-2
pii: 10.1038/s41698-024-00549-2
doi:
Types de publication
Journal Article
Langues
eng
Pagination
59Informations de copyright
© 2024. The Author(s).
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