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Patient derived tumoroids of high grade neuroendocrine neoplasms for more personalized therapies.
- Source :
- NPJ Precision Oncology; 3/1/2024, Vol. 8 Issue 1, p1-14, 14p
- Publication Year :
- 2024
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 2397768X
- Volume :
- 8
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- NPJ Precision Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 175829641
- Full Text :
- https://doi.org/10.1038/s41698-024-00549-2