@article{89e0a0cc61bb4c6c8b3e2389f9bcc17c,
title = "Combined Systemic Drug Treatment with Proton Therapy: Investigations on Patient-Derived Organoids",
abstract = "To optimize neoadjuvant radiochemotherapy of pancreatic ductal adenocarcinoma (PDAC), the value of new irradiation modalities such as proton therapy needs to be investigated in relevant preclinical models. We studied individual treatment responses to RCT using patient-derived PDAC organoids (PDO). Four PDO lines were treated with gemcitabine, 5-fluorouracile (5FU), photon and proton irradiation and combined RCT. Therapy response was subsequently measured via viability assays. In addition, treatment-naive PDOs were characterized via whole exome sequencing and tumorigenicity was investigated in NMRI Foxn1nu/nu mice. We found a mutational pattern containing common mutations associated with PDAC within the PDOs. Although we could unravel potential complications of the viability assay for PDOs in radiobiology, distinct synergistic effects of gemcitabine and 5FU with proton irradiation were observed in two PDO lines that may lead to further mechanistical studies. We could demonstrate that PDOs are a powerful tool for translational proton radiation research.",
keywords = "3D cell culture, PDAC, pancreatic cancer, patient-derived organoid, proton irradiation, radiochemotherapy, translational radiooncology",
author = "Max Naumann and Tabea Czempiel and L{\"o}{\ss}ner, {Anna Jana} and Kristin Pape and Elke Beyreuther and Steffen L{\"o}ck and Stephan Drukewitz and Alexander Hennig and {von Neubeck}, Cl{\"a}re and Barbara Klink and Mechthild Krause and Doreen William and Stange, {Daniel E.} and Rebecca B{\"u}tof and Antje Dietrich",
note = "Funding Information: This research was funded by the Kosing-Foundation and the European Union{\textquoteright}s H2020 Research and Innovation Programme under Grant Agreement No. 730983. Funding Information: In the past five years, Krause received funding for her research projects by Merck KGaA (2014–2018 for preclinical study; 2018–2020 for clinical study) and Medipan GmbH (2014–2018). She is involved in an ongoing, publicly funded (German Federal Ministry of Education and Research) project with the companies Medipan, Attomol GmbH, GA Generic Assays GmbH, Gesellschaft f{\"u}r medizinische und wissenschaftliche genetische Analysen, Lipotype GmbH, and PolyAn GmbH. For the present study, Krause confirms that none of the above-mentioned funding sources were involved. The other authors declare no conflict of interests. Publisher Copyright: {\textcopyright} 2022 by the authors.",
year = "2022",
month = aug,
day = "3",
doi = "10.3390/cancers14153781",
language = "English",
volume = "14",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "15",
}