Fig. 3: Biomarker validation in short-term patient-derived tumor cells (PDCs).

A Workflow depicting the generation of BC PDCs short-term ex vivo cultures from PDXs and the subsequent analysis of ribociclib response using two different read-outs. B Correlation analysis of the ex vivo response of PDCs (y-axis) vs. the in vivo response of the corresponding PDXs (x-axis), measured as change in spheroid area (open dots) or the change in EdU incorporation (filled dots) after ribociclib treatment. The Spearman’s coefficient (r), two-tailed p-value and 95% of confidence interval (95% CI) for each read-out are summarized below the graph. Representative images of one ribociclib-resistant (PDC039) and one ribociclib-sensitive (PDC244) model treated with vehicle or ribociclib are shown on the right panel, namely EdU/K18 staining by confocal microscopy and organoid size by bright field microscopy. EdU is shown in green, cytokeratin 18 (K18) in red and DAPI in blue. Scale bar = 100 µm. C Relative spheroid area in n = 14 PDC models classified as resistant (maroon) or sensitive (orange) according to the composite biomarker after treatment with 1 µM ribociclib for 7 days. Relative data to the vehicle control (100%) is represented as mean values of three independent experiments ± SEM; unpaired parametric t-test two-tailed p-value are indicated. D Concordance analysis of PDXs responses to ribociclib based on biomarker prediction (y-axis) vs. the ex vivo response (x-axis). Biomarkers are represented by circles with different colors and the number of PDX within each category is indicated. E ROC curve of the spheroid area increment for ribociclib response prediction in n = 37 BC PDCs. Unpaired t-test two-tailed p-value (<0.0001), the sensitivity, 95% confidence interval (95% CI) and specificity are summarized below the graph. Source data are provided as a Source Data file.