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Review
. 2025 Feb;13(1):21-33.
doi: 10.1002/ueg2.12701. Epub 2024 Nov 14.

Organoid-based precision medicine in pancreatic cancer

Affiliations
Review

Organoid-based precision medicine in pancreatic cancer

Alica K Beutel et al. United European Gastroenterol J. 2025 Feb.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) ranks among the leading causes of cancer-related deaths worldwide. Despite advances in precision oncology in other malignancies, treatment of PDAC still largely relies on conventional chemotherapy. Given the dismal prognosis and heterogeneity in PDAC, there is an urgent need for personalized therapeutic strategies to improve treatment response. Organoids, generated from patients' tumor tissue, have emerged as a powerful tool in cancer research. These three-dimensional models faithfully recapitulate the morphological and genetic features of the parental tumor and retain patient-specific heterogeneity. This review summarizes existing precision oncology approaches in PDAC, explores current applications and limitations of organoid cultures in personalized medicine, details preclinical studies correlating in vitro organoid prediction and patient treatment response, and provides an overview of ongoing organoid-based clinical trials.

Keywords: PDAC; drug response prediction; oncology; pancreatic ductal adenocarcinoma; patient‐derived organoids; personalized therapy; pharmacotyping; precision oncology; treatment response.

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Conflict of interest statement

T. Ettrich reports personal fees from MSD, Roche, Sanofi, BMS, AstraZeneca, Merck Serono, Pierre Fabre, Servier, Lilly, Ipsen, Daiichi Sankyo, AbbVie, Takeda, Amgen and grants from Servier, Lilly (Inst) outside of the submitted work. T. Seufferlein reports grants and personal fees from Celgene and Sanofi, personal fees from Amgen, AstraZeneca, Bayer, the Falk Foundation, Lilly, Merck‐Serono, Merck, Pierre Fabre, Roche, Servier, and Shire, and grants from Boehringer Ingelheim outside the submitted work. A. Kleger reports personal fees from the Falk foundation and Amgen outside the submitted work. No disclosures were reported by the other authors.

Figures

FIGURE 1
FIGURE 1
Study design of the UNITEPANC trial: Using organoids to predict efficacy of adjuvant treatment to improve outcome in resectable pancreatic cancer. The primary objectives are feasibility of selecting organoid‐based adjuvant treatment (Part I) and disease‐free survival at 18 months (Part II). DFS, disease‐free survival; mFOLFIRINOX, modified, 5‐fluorouracil, leucovorin, irinotecan, oxaliplatin; OS, overall survival; PDAC, pancreatic ductal adenocarcinoma.
FIGURE 2
FIGURE 2
Organoid‐based precision medicine in pancreatic cancer. Potential workflow to incorporate patient‐derived organoids into clinical care. Organoids can be generated from surgical resections and tissue or liquid biopsies from treatment‐naïve or pretreated PDAC patients. PDOs can be subjected to pharmacotyping and may inform treatment decisions. PDAC, pancreatic ductal adenocarcinoma; PDO, patient‐derived organoid. Source: Created with BioRender.com.

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