EMBO Molecular Medicine (Apr 2022)
Identification of treatment‐induced vulnerabilities in pancreatic cancer patients using functional model systems
- Katja Peschke,
- Hannah Jakubowsky,
- Arlett Schäfer,
- Carlo Maurer,
- Sebastian Lange,
- Felix Orben,
- Raquel Bernad,
- Felix N Harder,
- Matthias Eiber,
- Rupert Öllinger,
- Katja Steiger,
- Melissa Schlitter,
- Wilko Weichert,
- Ulrich Mayr,
- Veit Phillip,
- Christoph Schlag,
- Roland M Schmid,
- Rickmer F Braren,
- Bo Kong,
- Ihsan Ekin Demir,
- Helmut Friess,
- Roland Rad,
- Dieter Saur,
- Günter Schneider,
- Maximilian Reichert
Affiliations
- Katja Peschke
- Medical Clinic and Polyclinic II Klinikum rechts der Isar Technical University of Munich München Germany
- Hannah Jakubowsky
- Institute for Translational Cancer Research and Experimental Cancer Therapy Technical University of Munich Munich Germany
- Arlett Schäfer
- Medical Clinic and Polyclinic II Klinikum rechts der Isar Technical University of Munich München Germany
- Carlo Maurer
- Medical Clinic and Polyclinic II Klinikum rechts der Isar Technical University of Munich München Germany
- Sebastian Lange
- Medical Clinic and Polyclinic II Klinikum rechts der Isar Technical University of Munich München Germany
- Felix Orben
- Medical Clinic and Polyclinic II Klinikum rechts der Isar Technical University of Munich München Germany
- Raquel Bernad
- Medical Clinic and Polyclinic II Klinikum rechts der Isar Technical University of Munich München Germany
- Felix N Harder
- Institute of Diagnostic and Interventional Radiology Technical University of Munich Munich Germany
- Matthias Eiber
- Department of Nuclear Medicine Klinikum Rechts der Isar Technical University of Munich Munich Germany
- Rupert Öllinger
- Institute of Molecular Oncology and Functional Genomics TUM School of Medicine Technical University of Munich Munich Germany
- Katja Steiger
- Institute of Pathology Technical University of Munich München Germany
- Melissa Schlitter
- Institute of Pathology Technical University of Munich München Germany
- Wilko Weichert
- Institute of Pathology Technical University of Munich München Germany
- Ulrich Mayr
- Medical Clinic and Polyclinic II Klinikum rechts der Isar Technical University of Munich München Germany
- Veit Phillip
- Medical Clinic and Polyclinic II Klinikum rechts der Isar Technical University of Munich München Germany
- Christoph Schlag
- Medical Clinic and Polyclinic II Klinikum rechts der Isar Technical University of Munich München Germany
- Roland M Schmid
- Medical Clinic and Polyclinic II Klinikum rechts der Isar Technical University of Munich München Germany
- Rickmer F Braren
- Institute of Diagnostic and Interventional Radiology Technical University of Munich Munich Germany
- Bo Kong
- Department of Surgery Klinikum rechts der Isar Technical University of Munich Munich Germany
- Ihsan Ekin Demir
- Department of Surgery Klinikum rechts der Isar Technical University of Munich Munich Germany
- Helmut Friess
- Department of Surgery Klinikum rechts der Isar Technical University of Munich Munich Germany
- Roland Rad
- Institute of Molecular Oncology and Functional Genomics TUM School of Medicine Technical University of Munich Munich Germany
- Dieter Saur
- Institute for Translational Cancer Research and Experimental Cancer Therapy Technical University of Munich Munich Germany
- Günter Schneider
- Medical Clinic and Polyclinic II Klinikum rechts der Isar Technical University of Munich München Germany
- Maximilian Reichert
- Medical Clinic and Polyclinic II Klinikum rechts der Isar Technical University of Munich München Germany
- DOI
- https://doi.org/10.15252/emmm.202114876
- Journal volume & issue
-
Vol. 14,
no. 4
pp. n/a – n/a
Abstract
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.
Keywords
- functional screening
- pancreatic cancer
- precision oncology
- therapy‐induced vulnerabilities
- tumor cell plasticity
