In vitro and in vivo validation of screening hits
(A) Heatmap indicating drug response of commercially available 2D PDAC cell lines, PDAC organoid-derived monolayer lines, WT pancreas organoids, and PDAC organoids. Colors from red to blue represent normalized [%] viability compared to solvent (0.1% DMSO) control. Viability was screened at a dose of 1μM (red = high sensitivity, blue = low sensitivity). Data is represented as averages based on technical and biological replicates.
(B) Unsupervised clustering of different lines according to their drug response profile (green: WT pancreas organoid lines; red: PDAC organoid lines; orange: 2D PDAC cell lines).
(C) Growth curves represent the increase of relative tumor over the course of 21 days using the PC02-PDX model (n = 4–5 mice per group). The indicated statistical significance was computed using two-way ANOVA with Dunnett post hoc test.
(D) Relative tumor volume end of treatment period for the different groups. Data points represent individual mice used in the experiment. The indicated statistical significance was computed using one-way ANOVA with Dunnett post hoc test.
See also Figures S5, S6, and Table S7.