Detecting drug resistance in pancreatic cancer organoids guides optimized chemotherapy treatment

Research output: Contribution to journalResearch articleContributedpeer-review



Drug combination therapies for cancer treatment show high efficacy but often induce severe side effects, resulting in dose or cycle number reduction. We investigated the impact of neoadjuvant chemotherapy (neoCTx) adaptions on treatment outcome in 59 patients with pancreatic ductal adenocarcinoma (PDAC). Resections with tumor-free margins were significantly more frequent when full-dose neoCTx was applied. We determined if patient-derived organoids (PDOs) can be used to personalize poly-chemotherapy regimens by pharmacotyping of treatment-naïve and post-neoCTx PDAC PDOs. Five out of ten CTx-naïve PDO lines exhibited a differential response to either the FOLFIRINOX or the Gem/Pac regimen. NeoCTx PDOs showed a poor response to the neoadjuvant regimen that had been administered to the respective patient in 30% of cases. No significant difference in PDO response was noted when comparing modified treatments in which the least effective single drug was removed from the complete regimen. Drug testing of CTx-naïve PDAC PDOs and neoCTx PDOs may be useful to guide neoadjuvant and adjuvant regimen selection, respectively. Personalizing poly-chemotherapy regimens by omitting substances with low efficacy could potentially result in less severe side effects, thereby increasing the fraction of patients receiving a full course of neoadjuvant treatment.


Original languageEnglish
Pages (from-to)607-619
Number of pages13
JournalThe Journal of pathology
Issue number5
Publication statusPublished - Aug 2022

External IDs

WOS 000791050200001
Scopus 85129368032
Mendeley 54592b60-6d78-3c13-ba48-6915c537ab51
ORCID /0000-0002-9321-9911/work/142251953
ORCID /0000-0001-9389-4688/work/150330127
ORCID /0000-0001-7367-5525/work/151437319


Research priority areas of TU Dresden

Sustainable Development Goals


  • chemotherapy, pancreatic cancer, patient-derived organoids, personalized medicine, treatment response