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  • Identification of treatment-induced vulnerabilities in pancreatic cancer patients using functional model systems.

Identification of treatment-induced vulnerabilities in pancreatic cancer patients using functional model systems.

EMBO molecular medicine (2022-02-05)
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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-74, ascites fluid
Sigma-Aldrich
Cholera Toxin B subunit, ≥95% (SDS-PAGE), lyophilized powder
Sigma-Aldrich
TrypZean® Solution, 1×, recombinant, expressed in corn, sterile-filtered
Sigma-Aldrich
DAPI, for nucleic acid staining