Authors
Steven D Forsythe, Srujana V Yellapragada, Tracey Pu, Darryl Nousome, Samarth Mathur, Dilara Akbulut, Stephen G Andrews, Kamala A Kenny, Martha Quezado, Margaret C Cam, Jaydira Del Rivero, Serguei Kozlov, Jonathan M Hernandez, Naris Nilubol, James P Madigan, Samira M Sadowski
Published in
Science advances. Volume 12. Issue 30. Pages eaea4296. Jul 24, 2026. Epub Jul 24, 2026.
Abstract
Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are a rare subset of cancers with increasing incidence. Due to their slow growth and lack of targetable mutations, the identification of effective treatments remains limited. One reason behind this stagnation is the lack of applicable, accurate study models. One solution is patient tumor organoids (PTOs) that maintain tumor characteristics and can scale for high throughput assays. In this study, PTOs were generated from 35 tumors of pancreatic, small intestinal, and gastric origin, obtained from 17 patients. Important subtypes including hormone functional and MEN1/VHL mutant GEP-NETs are represented, with each demonstrating growth in culture while maintaining GEP-NET immunohistochemistry and genomic characteristics. Half of G2/G3 tumors (10 of 20) could be cultured past passage 6, whereas G1 tumors (n = 15) were capable of growth until passage 4. Therapeutic targeting of the PTOs displayed both tissue-origin and grade-based response to standard of care and investigational therapies while maintaining patient tumor sensitivity and resistance. Last, a successful PTO xenograft model was developed from one PTO line. This study describes GEP-NET organoid development that demonstrates feasibility for expansion, enabling their use for translational investigations.
PMID:
42497252
Bibliographic data and abstract were imported from PubMed on 25 Jul 2026.
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