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Updated: Jun 28, 2025
Multiparametric Tumor Organoid Drug Screening Using Widefield Live-Cell Imaging for Bulk and Single-Organoid Analysis
Published on: December 23, 2022
Establishment of Human Pituitary Neuroendocrine Tumor Derived Organoid and Its Pilot Application for Drug Screening
Run Cui1,2, Hao Duan1, Wanming Hu3
1Department of Neurosurgery/Neuro-Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, S Yat-Sen University Cancer Center, Guangzhou, 510060 Guangdong, China.
Context:
Precision medicine for pituitary neuroendocrine tumors (PitNETs) is limited by the lack of reliable research models.
Objective:
To generate patient-derived organoids (PDOs), which could serve as a platform for personalized drug screening for PitNET patients.
Design:
From July 2019 to May 2022, a total of 32 human PitNET specimens were collected for the establishment of organoids with an optimized culture protocol.
Setting:
This study was conducted at Sun Yat-Sen University Cancer Center.
Patients:
PitNET patients who were pathologically confirmed were enrolled in this study.
Interventions:
Histological staining and whole-exome sequencing were utilized to confirm the pathologic and genomic features of PDOs. A drug response assay on PDOs was also performed.
Main Outcome Measures:
PDOs retained key genetic and morphological features of their parental tumors.
Results:
PDOs were successfully established from various types of PitNET samples with an overall success rate of 87.5%. Clinical nonfunctioning PitNETs-derived organoids (22/23, 95.7%) showed a higher likelihood of successful generation compared to those from functioning PitNETs (6/9, 66.7%). Preservation of cellular structure, subtype-specific neuroendocrine profiles, mutational features, and tumor microenvironment heterogeneity from parental tumors was observed. A distinctive response profile in drug tests was observed among the organoids from patients with different subtypes of PitNETs. With the validation of key characteristics from parental tumors in histological, genomic, and microenvironment heterogeneity consistency assays, we demonstrated the predictive value of the PDOs in testing individual drugs.
Conclusion:
The established PDOs, retaining typical features of parental tumors, indicate a translational significance in innovating personalized treatment for refractory PitNETs.
Insights
Patient-derived organoids (PDOs) were successfully generated from pituitary neuroendocrine tumors (PitNETs). These PDOs accurately model patient tumors, offering a platform for personalized drug screening and treatment strategies.
Area of Science:
- Oncology
- Translational Research
- Genomics
Background:
- Precision medicine for pituitary neuroendocrine tumors (PitNETs) is hindered by a lack of reliable research models.
- Developing patient-specific models is crucial for advancing personalized treatment strategies.
Purpose of the Study:
- To establish patient-derived organoids (PDOs) from PitNET specimens.
- To create a platform for personalized drug screening in PitNET patients.
Main Methods:
- Collected 32 human PitNET specimens between July 2019 and May 2022.
- Utilized an optimized culture protocol for organoid establishment.
- Confirmed PDO features using histological staining and whole-exome sequencing; performed drug response assays.
Main Results:
- Achieved an 87.5% success rate in establishing PDOs from various PitNET types.
- PDOs successfully retained key genetic, morphological, and tumor microenvironment features of parental tumors.
- Demonstrated distinct drug response profiles among PDOs, validating their predictive value for personalized medicine.
Conclusions:
- Established PDOs serve as a valuable translational tool for PitNET research.
- These models hold significant potential for innovating personalized treatment strategies for refractory PitNETs.
