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Updated: Oct 4, 2025
Establishment of Zebrafish Patient-Derived Xenografts from Pancreatic Cancer for Chemosensitivity Testing
Published on: May 12, 2023
Identification of treatment-induced vulnerabilities in pancreatic cancer patients using functional model systems
Katja Peschke1, Hannah Jakubowsky2, Arlett Schäfer1
1Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
Abstract:
Despite the advance and success of precision oncology in gastrointestinal cancers, the frequency of molecular-informed therapy decisions in pancreatic ductal adenocarcinoma (PDAC) is currently neglectable. We present a longitudinal precision oncology platform based on functional model systems, including patient-derived organoids, to identify chemotherapy-induced vulnerabilities. We demonstrate that treatment-induced tumor cell plasticity in vivo distinctly changes responsiveness to targeted therapies, without the presence of a selectable genetic marker, indicating that tumor cell plasticity can be functionalized. By adding a mechanistic layer to precision oncology, adaptive processes of tumors under therapy can be exploited, particularly in highly plastic tumors, such as pancreatic cancer.
Insights
Precision oncology in pancreatic cancer is limited. This study uses patient-derived organoids to reveal how tumor cell plasticity affects chemotherapy response, offering new therapeutic strategies.
Area of Science:
- Oncology
- Cancer Biology
- Translational Medicine
Background:
- Precision oncology has advanced gastrointestinal cancer treatment, but its application in pancreatic ductal adenocarcinoma (PDAC) remains limited.
- Molecular-informed therapy decisions are currently underutilized in PDAC management.
- Pancreatic cancer is characterized by high tumor cell plasticity, posing challenges for effective treatment.
Purpose of the Study:
- To develop a longitudinal precision oncology platform using functional model systems, including patient-derived organoids.
- To identify chemotherapy-induced vulnerabilities in pancreatic ductal adenocarcinoma.
- To investigate the role of tumor cell plasticity in therapeutic response.
Main Methods:
- Establishment of a precision oncology platform utilizing patient-derived organoids.
- Longitudinal monitoring of tumor cell responses to chemotherapy.
- In vivo validation of treatment-induced changes in tumor cell plasticity and therapy responsiveness.
Main Results:
- The platform successfully identified chemotherapy-induced vulnerabilities in pancreatic cancer models.
- Treatment-induced tumor cell plasticity was shown to alter responsiveness to targeted therapies, independent of genetic markers.
- Tumor cell plasticity was demonstrated to be a functional target for therapeutic intervention.
Conclusions:
- A novel precision oncology platform based on functional models can uncover treatment vulnerabilities in pancreatic cancer.
- Exploiting tumor cell plasticity, particularly in adaptive cancer processes, offers a promising strategy for improving therapeutic outcomes.
- This approach enhances precision oncology by incorporating a mechanistic understanding of tumor adaptation under therapy.
