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Updated: Aug 6, 2026
Cultivating Ex Vivo Patient-Derived Glioma Organoids Using a Tissue Chopper
Published on: January 19, 2024
Expanded GEP-NET organoid culture for personalized therapy evaluation
Steven D Forsythe1, Srujana V Yellapragada1, Tracey Pu2
1Neuroendocrine Cancer Therapy Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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.
Insights
Patient tumor organoids (PTOs) offer a new way to study rare gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). These models accurately reflect patient tumors, enabling personalized therapeutic strategies.
Area of Science:
- Oncology
- Gastroenterology
- Cancer Biology
Background:
- Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are rare cancers with limited treatment options due to slow growth and lack of targetable mutations.
- The absence of accurate and applicable study models hinders progress in GEP-NET research and therapeutic development.
Purpose of the Study:
- To develop and characterize patient tumor organoids (PTOs) from GEP-NETs for use in translational research.
- To assess the feasibility of culturing and expanding GEP-NET PTOs while maintaining their key characteristics.
- To evaluate the potential of PTOs as models for therapeutic targeting and personalized medicine.
Main Methods:
- Generation of patient tumor organoids (PTOs) from 35 GEP-NET tumors across pancreatic, small intestinal, and gastric origins.
- Characterization of PTOs through immunohistochemistry and genomic profiling to confirm maintenance of GEP-NET features.
- Assessment of PTO growth kinetics across different tumor grades (G1, G2/G3) and passages.
- Evaluation of therapeutic responses in PTOs to standard of care and investigational agents.
- Development of a patient tumor organoid xenograft model.
Main Results:
- Successful establishment of GEP-NET PTOs from diverse tumor origins and subtypes, including hormone-functional and *MEN1*/*VHL* mutant tumors.
- PTOs maintained key immunohistochemical and genomic characteristics of the original patient tumors.
- Tumor grade influenced the cultureability of PTOs, with G1 tumors growing to passage 4 and half of G2/G3 tumors cultured past passage 6.
- PTOs accurately reflected patient tumor sensitivity and resistance profiles when tested with various therapies.
- A functional PTO xenograft model was successfully developed.
Conclusions:
- GEP-NET patient tumor organoids are feasible to develop and expand, serving as valuable preclinical models.
- These organoids maintain critical patient-specific tumor characteristics, enabling the study of GEP-NET biology and drug response.
- The development of GEP-NET PTOs facilitates translational investigations and the exploration of personalized therapeutic strategies for these rare cancers.
