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Updated: Jan 2, 2026
Author Spotlight: Establishment of Pancreatic Cancer-Derived Tumor Organoids and Fibroblasts From Fresh Tissue
Published on: May 26, 2023
Pancreatic cancer organoids recapitulate disease and allow personalized drug screening
Else Driehuis1,2, Arne van Hoeck1,3, Kat Moore4
1Oncode Institute, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Abstract:
We report the derivation of 30 patient-derived organoid lines (PDOs) from tumors arising in the pancreas and distal bile duct. PDOs recapitulate tumor histology and contain genetic alterations typical of pancreatic cancer. In vitro testing of a panel of 76 therapeutic agents revealed sensitivities currently not exploited in the clinic, and underscores the importance of personalized approaches for effective cancer treatment. The PRMT5 inhibitor EZP015556, shown to target MTAP (a gene commonly lost in pancreatic cancer)-negative tumors, was validated as such, but also appeared to constitute an effective therapy for a subset of MTAP-positive tumors. Taken together, the work presented here provides a platform to identify novel therapeutics to target pancreatic tumor cells using PDOs.
Insights
Patient-derived organoids (PDOs) from pancreatic and bile duct tumors reveal new therapeutic targets. This platform identifies novel treatments for pancreatic cancer, emphasizing personalized medicine approaches.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Biology
Background:
- Pancreatic cancer and distal bile duct tumors present significant therapeutic challenges.
- Patient-derived organoids (PDOs) offer a promising preclinical model for studying tumor biology and drug response.
- Genetic alterations in pancreatic cancer, such as MTAP loss, influence treatment efficacy.
Purpose of the Study:
- To establish and characterize patient-derived organoid (PDO) lines from pancreatic and distal bile duct tumors.
- To screen a panel of therapeutic agents in PDOs to identify novel treatment strategies.
- To validate the efficacy of a PRMT5 inhibitor (EZP015556) in targeting pancreatic tumors, including MTAP-altered and MTAP-positive cases.
Main Methods:
- Derivation of 30 PDO lines from patient tumors.
- Characterization of PDOs for recapitulation of tumor histology and genetic alterations.
- In vitro drug screening of 76 therapeutic agents against PDOs.
- Validation of PRMT5 inhibitor EZP015556 efficacy in MTAP-negative and MTAP-positive PDOs.
Main Results:
- PDOs successfully recapitulated the histology and genetic landscape of the original tumors.
- Drug screening identified potential therapeutic sensitivities not currently utilized in clinical practice.
- The PRMT5 inhibitor EZP015556 demonstrated efficacy in MTAP-negative tumors and a subset of MTAP-positive tumors.
- The study highlights the potential for personalized therapeutic strategies in pancreatic cancer.
Conclusions:
- PDOs serve as a valuable platform for discovering and validating novel pancreatic cancer therapeutics.
- Personalized approaches, guided by PDO drug screening, are crucial for effective pancreatic cancer treatment.
- Targeting PRMT5 with agents like EZP015556 shows promise for a broader range of pancreatic tumors than initially anticipated.
