Fig. 1
TGMO-based screen for cell line specific ODCs in CRC 3D complex models. A Initial selection of drugs used in the TGMO-based screen B. Schematic representation of the TGMO platform. Regression coefficients generated from search 3 of single drug 1st order, drug-drug and single drug 2nd order drug interactions (red, burgundy and pink lines, respectively) in C 3DccSW620 D 3DccLS174T (green/orange bars respectively) and the therapeutic window (stripped black bars). E Schematic representation of the generation of complex CRC FOLFOXIRI resistant 3D models, 3D-FXLSFXR and 3D-FXSWFXR and respective ODC identification. F 3D-FXSWFXR and G 3D-FXLSFXR (solid green/orange squared bars respectively) in the left panel. In yellow is highlighted the most robust drug interaction that is maintained in each final ODC. In the corresponding right panels, the activity of the ODCs, corresponding monotherapies (colored bars) and FOLFOXIRI (folinic acid [0.5 µM], 5-FU [10 µM], SN38 [0.1 µM] and oxaliplatin [0.5 µM], red bars) in CRC 3D models, and activity in 3DccCCD841 (stripped black bars) used to generate the therapeutic window (TW). Activity is measured by ATP levels vs. CTRL (< 0.15% DMSO). Data are presented as the mean of N = 2–3 independent experiments, error bars represent SD. Significance is determined by one-way ANOVA (regression models, left panel) and two-way ANOVA (activity graphs, right panel) with *p < 0.05, **p < 0.01 and ***p < 0.001