Journal Article

DKFZ-2025-01907

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Multi-drug pharmacotyping improves therapy prediction in pancreatic cancer organoids.

Wansch, K. ; Pelzer, U. ; Schneider, F. ; Dölvers, F. ; Kühn, A. ; Dragomir, M.-P.DKFZ* ; Ihlow, J. ; Hilfenhaus, G. ; Vecchione, L. ; Felsenstein, M. ; Ma, D. ; Lerchbaumer, M. ; Jürgensen, C. ; Bahra, M. ; Granada, A. E. ; Duwe, G. ; Stintzing, S. ; Keilholz, U. ; Neumann, C. C. M.

2025
BioMed Central London

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Please use a persistent id in citations: doi:10.1186/s12935-025-03969-7

Abstract: Patient-Derived Organoids (PDOs) represent a promising technology for therapy prediction in pancreatic cancer, with the potential of enhancing treatment outcomes and allowing more effective, personalized treatment choices. However, classification approaches into sensitive and resistant models remain very variable and are based on single-agent testing only, neglecting interactive effects of multi-drug combinations. Here, we established 13 PDOs and performed both single-agent and multi-drug testing. By comparing different clustering approaches of drug-response metrics and establishing a new classification approach based on pharmacokinetic modelling, we were able to evaluate which score best predicts the clinical response of patients. Our newly developed score considered the Area Under The Curve (AUC) of cell viability curves and reached a prediction accuracy of 85%. Our data supports previous findings for PDOs to constitute an effective platform for translational drug testing. Furthermore, our results suggest that the AUC is a more accurate drug-response metric than the half maximal inhibitory concentration (IC50), and that multi-drug testing yields a higher accuracy than single-agent testing. The methodology and outcomes presented in this study are of critical relevance for future PDO-based translational trials as they allow a new physiology-based approach towards multi-drug testing and classification of organoid response, which improves PDO prediction accuracy.

Keyword(s): Multi-Drug response metrics ; Pancreatic adenocarcinoma ; Patient-derived organoids ; Pharmacokinetic modelling

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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