Combination of ribociclib and gemcitabine decreases the activity of genes involved in cell cycle regulation and DNA damage response in MB002 tumors. Mice bearing human MB002 PDOX treated with vehicle (black bar), gemcitabine (60 mg/kg, blue bar), ribociclib (100 mg/kg, red bar) or both (purple bar). Tumors were harvested on day 5 after short term treatment (A–C) or after long-term treatment at moribund stage (D–F). A and D, NetBID analysis to infer gene activity from RNA-seq data and a MB-specific interactome. Activity heatmaps of a selection of genes in tumors from the four treatment groups. B and E, Volcano plots showing genes with differential activity between tumors treated with gemcitabine and ribociclib versus vehicle (network size > 25; P < 0.01 and logFC < -0.05 or logFC > 0.05). C and F, Clustering of genes involved in down-regulated pathways. G, Venn diagram showing the number of differentially expressed genes from tumors treated with gemcitabine and ribociclib versus vehicle between short-term and long-term treatments.