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Updated: Nov 11, 2025
Human Neural Organoids for Studying Brain Cancer and Neurodegenerative Diseases
Published on: June 28, 2019
Patient-Derived Organoid Models of Human Neuroendocrine Carcinoma
Krijn K Dijkstra1,2, José G van den Berg3, Fleur Weeber1,2
1Department of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands.
Abstract:
Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a poorly understood disease with limited treatment options. A better understanding of this disease would greatly benefit from the availability of representative preclinical models. Here, we present the potential of tumor organoids, three-dimensional cultures of tumor cells, to model GEP-NEC. We established three GEP-NEC organoid lines, originating from the stomach and colon, and characterized them using DNA sequencing and immunohistochemistry. Organoids largely resembled the original tumor in expression of synaptophysin, chromogranin and Ki-67. Models derived from tumors containing both neuroendocrine and non-neuroendocrine components were at risk of overgrowth by non-neuroendocrine tumor cells. Organoids were derived from patients treated with cisplatin and everolimus and for the three patients studied, organoid chemosensitivity paralleled clinical response. We demonstrate the feasibility of establishing NEC organoid lines and their potential applications. Organoid culture has the potential to greatly extend the repertoire of preclinical models for GEP-NEC, supporting drug development for this difficult-to-treat tumor type.
Insights
Tumor organoids offer a promising new model for studying gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC). These GEP-NEC organoid lines show potential for preclinical research and drug development for this challenging cancer.
Area of Science:
- Oncology
- Gastroenterology
- Cancer Biology
Background:
- Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is poorly understood with limited therapeutic strategies.
- Development of representative preclinical models is crucial for advancing GEP-NEC research.
- Tumor organoids, as three-dimensional cell cultures, present a novel approach for disease modeling.
Purpose of the Study:
- To establish and characterize GEP-NEC organoid lines for preclinical modeling.
- To assess the fidelity of organoids in representing the original tumor characteristics.
- To evaluate the potential of organoids in predicting patient response to chemotherapy.
Main Methods:
- Establishment of three GEP-NEC organoid lines from stomach and colon tumors.
- Characterization using DNA sequencing and immunohistochemistry (synaptophysin, chromogranin, Ki-67).
- Assessment of organoid chemosensitivity against clinical response to cisplatin and everolimus.
Main Results:
- GEP-NEC organoid lines were successfully established, reflecting original tumor expression profiles.
- Potential overgrowth of non-neuroendocrine components in mixed tumors was observed.
- Organoid chemosensitivity correlated with clinical responses in three patient-derived models.
Conclusions:
- Organoid culture is a feasible method for generating GEP-NEC preclinical models.
- These organoids can accurately model GEP-NEC and support drug discovery efforts.
- Organoid models offer a valuable tool to improve treatment strategies for GEP-NEC.
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