The Journal of clinical endocrinology and metabolism · 2025
Establishment of Human Pituitary Neuroendocrine Tumor Derived Organoid and Its Pilot Application for Drug Screening.
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Cui Run, Duan Hao, Hu Wanming, Li Chang, Zhong Sheng, Liang Lun, Chen Siyu, Hu Hongrong, He Zhenqiang, Wang Zhenning, Guo Xiaoyu, Chen Zexin, Xu Cong, Zhu Yu, Chen Yinsheng, Sai Ke, Yang Qunying, Guo Chengcheng, Mou Yonggao, Jiang Xiaobing
Аннотация
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.
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.