Naumann Max, Czempiel Tabea, Lößner Anna Jana, Pape Kristin, Beyreuther Elke, Löck Steffen, Drukewitz Stephan, Hennig Alexander, von Neubeck Cläre, Klink Barbara, Krause Mechthild, William Doreen, Stange Daniel E, Bütof Rebecca, Dietrich Antje
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.
Cancers (Basel). 2022 Aug 3;14(15):3781. doi: 10.3390/cancers14153781.
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 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.
为优化胰腺导管腺癌（PDAC）的新辅助放化疗，需要在相关临床前模型中研究质子治疗等新放疗模式的价值。我们使用患者来源的PDAC类器官（PDO）研究了对放化疗联合治疗（RCT）的个体治疗反应。四条PDO系分别接受吉西他滨、5-氟尿嘧啶（5FU）、光子和质子照射以及放化疗联合治疗。随后通过活力测定法测量治疗反应。此外，通过全外显子测序对未经治疗的PDO进行表征，并在NMRI Foxn1小鼠中研究其致瘤性。我们在PDO中发现了一种包含与PDAC相关常见突变的突变模式。虽然我们可以揭示放放射生物学中PDO活力测定的潜在并发症，但在两条PDO系中观察到吉西他滨和5FU与质子照射有明显的协同效应，这可能会促使进一步的机制研究。我们可以证明，PDO是转化质子辐射研究的有力工具。
