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 #

. 2022 doi: 10.15252/emmm.202114876


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.