Combined Systemic Drug Treatment with Proton Therapy: Investigations on Patient-Derived Organoids.

Autor: Naumann M; OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany.; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany., Czempiel T; Core Unit for Molecular Tumor Diagnostics (CMTD), National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany., Lößner AJ; Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany., Pape K; Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany., Beyreuther E; OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany.; Institute of Radiation Physics, Helmholtz-Zentrum Dresden-Rossendorf, 01328 Dresden, Germany., Löck S; OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany.; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.; National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany.; German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), 69192 Heidelberg, Germany.; Institute of Radiooncology-OncoRay, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany., Drukewitz S; Core Unit for Molecular Tumor Diagnostics (CMTD), National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany.; Institute of Human Genetics, University of Leipzig Medical Center, 04103 Leipzig, Germany., Hennig A; Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.; National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany., von Neubeck C; OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany.; German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), 69192 Heidelberg, Germany.; Clinic for Particle Therapy, University Hospital Essen, Universität Duisburg Essen, 45147 Essen, Germany., Klink B; Core Unit for Molecular Tumor Diagnostics (CMTD), National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany.; Department of Genetics, Laboratoire National de Santé, 3555 Dudelange, Luxembourg.; Institute for Clinical Genetics, University Hospital Carl Gustav Carus, Technische Universität Dresden, ERN-GENTURIS, Hereditary Cancer Syndrome Center Dresden, 01307 Dresden, Germany., Krause M; OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany.; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.; National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany.; German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), 69192 Heidelberg, Germany.; Institute of Radiooncology-OncoRay, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany., William D; Core Unit for Molecular Tumor Diagnostics (CMTD), National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany.; Institute for Clinical Genetics, University Hospital Carl Gustav Carus, Technische Universität Dresden, ERN-GENTURIS, Hereditary Cancer Syndrome Center Dresden, 01307 Dresden, Germany., Stange DE; Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.; National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany., Bütof R; OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany.; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.; National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany.; Institute of Radiooncology-OncoRay, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany., Dietrich A; OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany.; German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), 69192 Heidelberg, Germany.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 Aug 03; Vol. 14 (15). Date of Electronic Publication: 2022 Aug 03.
DOI: 10.3390/cancers14153781
Abstrakt: 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 Foxn1 nu/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.
Databáze: MEDLINE
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