Journal
EMBO MOLECULAR MEDICINE
Volume 14, Issue 4, Pages -Publisher
WILEY
DOI: 10.15252/emmm.202114876
Keywords
functional screening; pancreatic cancer; precision oncology; therapy-induced vulnerabilities; tumor cell plasticity
Categories
Funding
- Deutsche Forschungsgemeinschaft (DFG)-SFB1321 [329628492, S01, P13]
- Deutsche Krebshilfe [70113760]
- Wilhelm Sander Stiftung [2017.048.2, 2019.086.1]
- Deutsche Krebshilfe (Max-Eder Program) [111273]
- DFG [RE 3723/4-1]
- ProjektDEAL
- [DFG-SFB824]
- [C9]
- [DFG-SCHN959/3-2]
- [SCHN959/6-1]
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This article introduces a longitudinal precision oncology platform based on functional model systems to identify chemotherapy-induced vulnerabilities in pancreatic ductal adenocarcinoma (PDAC). It is found that treatment-induced tumor cell plasticity distinctly changes responsiveness to targeted therapies.
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.
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