Implementing cell-free DNA of pancreatic cancer patient–derived organoids for personalized oncology

• DOI: 10.1172/jci.insight.137809
• Publication Date: 2020-07-02T16:01:48Z
• Authors: Zahra Dantes; Hsi-Yu Yen; Nicole Pfarr; Christof Winter; Katja Steiger; Alexander Muckenh...; Alexander Hennig; Sebastian Lange; Thomas Engleitner; Rupert Öllinger; Roman Maresch; Felix Orben; Irina Heid; Georgios Kaissis; Kuangyu Shi; Geoffrey Topping; Fabian Stögbauer; Matthias Wirth; Katja Peschke; Aristeidis Paparg...; Massoud Rezaee-Og...; Karin Feldmann; Arlett P.G. Schäfer; Raphela Ranjan; Clara Lubeseder-M...; Daniel E. Stange; Thilo Welsch; Marc Martignoni; Güralp O. Ceyhan; Helmut Friess; Alexander Herner; Lucia Liotta; Matthias Treiber; Guido von Figura; Mohamed Abdelhafez; Peter Klare; Christoph Schlag; Hana Algül; Jens Siveke; Rickmer Braren; Gregor Weirich; Wilko Weichert; Dieter Saur; Roland Rad; Roland M. Schmid; Günter Schneider; Maximilian Reichert
• Keywords: Organoid; Personalized Medicine; Liquid biopsy; Cell-free fetal DNA; Clinical Oncology

One of the major challenges in using pancreatic cancer patient–derived organoids (PDOs) precision oncology is time from biopsy to functional characterization. This particularly true for endoscopic ultrasound-guided fine-needle aspiration biopsies, typically resulting specimens with limited tumor cell yield. Here, we tested conditioned media individual PDOs cell-free DNA detect driver mutations already early on during expansion process accelerate genetic characterization as well subsequent testing. Importantly, alterations detected PDO supernatant, collected 72 hours after biopsy, recapitulate mutational profile primary tumor, indicating suitability this approach subject drug testing a reduced frame. In addition, demonstrated that workflow was practicable, even patients whom amount material not sufficient molecular by established means. Together, our findings demonstrate generating very permits profiling and With approach, can be achieved rapid feasible fashion broad implications clinical practice.