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Updated: Aug 13, 2025
Isolation and Characterization of Patient-derived Pancreatic Ductal Adenocarcinoma Organoid Models
Published on: January 14, 2020
Exploration of Patient-Derived Pancreatic Ductal Adenocarcinoma Ex Vivo Tissue for Treatment Response
Tímea Szekerczés1, Arun Kumar Selvam1, Carlos Fernández Moro1,2
1Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, 141 52 Huddinge, Sweden.
Abstract:
Patient-derived tissue culture models are valuable tools to investigate drug effects and targeted treatment approaches. Resected tumor slices cultured ex vivo have recently gained interest in precision medicine, since they reflect the complex microenvironment of cancer tissue. In this study, we examined the treatment response to an internally developed ex vivo tissue culture model from pancreatic ductal adenocarcinoma (PDAC) and in vitro analysis. Seven PDAC tissues were cultured and subsequently treated with indole-3-pyruvic acid (IPA). IPA, which is known as an agonist of the aryl hydrocarbon receptor (AHR) pathway, has antioxidant properties. Genome-wide transcriptome sequencing analysis revealed activation of AHR pathway genes (CYP1A1 and CYP1B1, p ≤ 0.05). Additionally, significant upregulation of AHR repressor genes AHRR and TiPARP was also observed (p ≤ 0.05), which is indicative of the negative feedback loop activation of AHR pathway signaling. The overall transcriptomic response to IPA indicated that the tissues are biologically active and respond accordingly to exogenous treatment. Cell culture analysis confirmed the significant induction of selected AHR genes by IPA. A morphological examination of the paraffin-embedded formalin-fixed tissue did not show obvious signs of IPA treatment related to tumor cell damage. This study is a proof of concept that ex vivo patient-derived tissue models offer a valuable tool in precision medicine to monitor the effect of personalized treatments.
Insights
This study demonstrates that patient-derived ex vivo tissue models effectively monitor drug responses in pancreatic cancer. Indole-3-pyruvic acid (IPA) activated specific pathways, proving the model
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Patient-derived tissue culture models are crucial for precision medicine.
- Ex vivo tumor slice cultures preserve the cancer microenvironment.
- Pancreatic ductal adenocarcinoma (PDAC) requires novel treatment strategies.
Purpose of the Study:
- To evaluate an ex vivo tissue culture model for pancreatic ductal adenocarcinoma (PDAC).
- To assess the treatment response of PDAC tissue to indole-3-pyruvic acid (IPA).
- To investigate the activation of the aryl hydrocarbon receptor (AHR) pathway by IPA.
Main Methods:
- Seven PDAC tissue samples were cultured ex vivo.
- Tissues were treated with indole-3-pyruvic acid (IPA).
- Genome-wide transcriptome sequencing and cell culture analysis were performed.
Main Results:
- IPA treatment activated AHR pathway genes (CYP1A1, CYP1B1) and feedback repressors (AHRR, TiPARP).
- Transcriptomic analysis confirmed biological activity and response to IPA.
- Cell cultures showed significant induction of AHR genes by IPA.
- No significant tumor cell damage was observed morphologically.
Conclusions:
- Ex vivo patient-derived tissue models are viable for monitoring personalized treatment effects.
- IPA demonstrates potential as an AHR pathway modulator in PDAC.
- This model serves as a proof of concept for precision medicine applications.
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