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

Max Naumann, Tabea Czempiel, Anna Jana Lößner, Kristin Pape, Elke Beyreuther, Steffen Löck, Stephan Drukewitz, Alexander Hennig, Cläre von Neubeck, Barbara Klink, Mechthild Krause, Doreen William, Daniel E. Stange, Rebecca Bütof, Antje Dietrich*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article number3781
JournalCancers
Volume14
Issue number15
DOIs
Publication statusPublished - 3 Aug 2022
Externally publishedYes

Keywords

  • 3D cell culture
  • pancreatic cancer
  • patient-derived organoid
  • PDAC
  • proton irradiation
  • radiochemotherapy
  • translational radiooncology

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