Multi-drug pharmacotyping improves therapy prediction in pancreatic cancer organoids

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 (IC<sub>50</sub>), 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.

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Publication Details

Journal
Cancer Cell International
Published
2025-09-13
DOI
https://doi.org/10.1186/s12935-025-03969-7
Citations
1
Primary Topic
Pancreatic and Hepatic Oncology Research
Type
article
Field-Weighted Citation Impact
1.05
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article

Multi-drug pharmacotyping improves therapy prediction in pancreatic cancer organoids

Uwe Pelzer, Marcus Bahra, Sebastian Stintzing, Markus Herbert Lerchbaumer et al.
1 citations
Cancer Cell International
Pancreatic and Hepatic Oncology Research
1.05
article

Multi-drug pharmacotyping improves therapy prediction in pancreatic cancer organoids

Uwe Pelzer, Marcus Bahra, Sebastian Stintzing, Markus Herbert Lerchbaumer, Anna Luisa Kühn, Jana Ihlow, F Schneider, Matthäus Felsenstein, Gregor Duwe, Mihnea P. Dragomir, Dong Ma, Georg Hilfenhaus, Ulrich Keilholz, Christopher Neumann, Adrián E. Granada, Loredana Vecchione, Christian Jürgensen, Katharina Wansch, Florian Dölvers
article en
1 citations

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 (IC<sub>50</sub>), 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.

Cancer Cell InternationalVol. 25(1)
German Cancer Research Center (DE), Johannes Gutenberg University Mainz (DE), Heidelberg University (DE), Humboldt-Universität zu Berlin (DE), University Medical Center of the Johannes Gutenberg University Mainz (DE), Krankenhaus Waldfriede (DE), Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE), Freie Universität Berlin (DE), Charité - Universitätsmedizin Berlin (DE)
Openalex Percentile: Top 18%
Pancreatic and Hepatic Oncology Research
1.05
DOIOpen Access PDFOpenAlex
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