Patient derived tumoroids of high grade neuroendocrine neoplasms for more personalized therapies

Patient derived tumoroids of high grade neuroendocrine neoplasms for more personalized therapies

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 advan...

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Published in:NPJ precision oncology Vol. 8; no. 1; p. 59
Main Authors: April-Monn, Simon L., Kirchner, Philipp, Detjen, Katharina, Bräutigam, Konstantin, Trippel, Mafalda A., Grob, Tobias, Statzer, Cyril, Maire, Renaud S., Kollàr, Attila, Chouchane, Aziz, Kunze, Catarina A., Horst, David, Sadowski, Martin C., Schrader, Jörg, Marinoni, Ilaria, Wiedenmann, Bertram, Perren, Aurel
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01-03-2024
Nature Publishing Group
Nature Portfolio
Subjects:
692/4028
692/4028/67
692/4028/67/1459
692/4028/67/1459/1963
Biobanks
Biomarkers
Cancer Research
Chemotherapy
Gene Therapy
Human Genetics
Internal Medicine
Medicine
Medicine & Public Health
Metastasis
Mutation
Neuroendocrine tumors
Oncology
Patients
Targeted cancer therapy
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Summary: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.
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ISSN:2397-768X
2397-768X
DOI:10.1038/s41698-024-00549-2