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Article History

Received: 10 December 2024

Accepted: 24 March 2025

First Online: 3 April 2025

Declarations

:

: The Ethics Committee of Friedrich-Alexander University Erlangen-Nürnberg (FAU), Germany, approved the use of human pancreatic tissue samples for this study (No. 16-167Bc). All procedures involving human pancreatic tissue samples were conducted in compliance with the ethical standards of the institutional research committee. According to the Ethics Committee, informed consent was not required from individual participants because the data analyzed in this study were anonymized and did not contain any personally identifiable information.

: Not applicable.

: The authors declare no competing interests.

: The online version contains supplementary material available at.Additional file 1: Table Culture media and their applications for specific cell types, Table S2 Cytotoxic effects of chemotherapeutic agents on KRAS G12D knockout cells, Table S3 Cytotoxic effects of jorunnamycin A and oxaliplatin on KRAS G12D knockout cells, Table S4 Inhibitory effects of jorunnamycin A and oxaliplatin on KRAS G12D knockout spheroids, Table S5 KRAS nucleotide sequences retrieved from patient-derived tumor and normal organoids, Fig. . Docking validation and RMSD value of the KRAS G12D binding site, Fig. S2. NMR chromatograms and LC-MS purity analysis of jorunnamycin A, Fig. S3. Validation of KRAS mutations (G12D, G12C, and G12V) and CRISPR/Cas9 knockout of KRAS G12D in pancreatic cancer cell lines via western blot analysis, Fig. S4. Cytotoxic profiles of jorunnamycin A in pancreatic cancer and normal cells, Fig. S5. Combination effect of jorunnamycin A and SN-38 in KRAS G12D pancreatic cancer cells, Fig. S6. Combination effect of jorunnamycin A and paclitaxel in KRAS G12D pancreatic cancer cells, Fig. S7. Combination effect of jorunnamycin A and 5-fluorouracil in KRAS G12D pancreatic cancer cells, Fig. S8. Combination effect of jorunnamycin A (JA) and gemcitabine (GEM) in KRAS G12D pancreatic cancer cells. Fig. S9. Variation in KRAS mutations in patient-derived organoids assessed by western blot analysis, Fig. . Morphological characteristics of patient-derived organoids following treatments with jorunnamycin A and oxaliplatin, and Figs. S11, S12, S13 and S14. Original protein bands visualized by western blot analysis supporting Figs. 3, 4 and 7, and 10 of this study.