Fig. 2: IGF1R confers resistance to GDC0032.
A Bar graph showing the nine shared enriched upregulated pathways, scored by averaging the KEGG combined scores for each pathway of each cell line. B A scheme illustrating the synthetic lethality shRNA screen workflow, done on IGROV1Res cells. C Volcano plot visualizing the results (log2 fold change against –log10 p value) for the comparison between those cells treated with GDC0032 and the control cells. Each dot corresponds to one shRNA. Genes with at least two shRNAs with significant differential expression that were all consistently either up- or downregulated are denoted in color (see the color index). D Heatmap across all samples displaying the top 30 differentially expressed shRNAs. Colors on the right indicate the genes, and match the color index of the former panel (2 C). E A drug matrix showing the sensitivity of IGROV1Res cells to multiple inhibitors, combined with increasing concentrations of GDC0032. F The inhibitory effect of each drug was calculated for both IGROV1Res and OAW42Res in the presence of 0.5 uM of GDC0032. Inhibitors that had a higher effect than GDC0032 alone for both cell lines are in the red quartile. G A dose matrix used to calculate the synergistic effect of combining GDC0032 and AEW541. The concentration of AEW541 increases from the bottom to the top and the concentration of GDC0032 from the left to the right. H Scatter plot showing the mRNA levels of IGF1R before and after GDC0032 treatment for both IGROV1 and OAW42, sensitive (black) and resistant (red) cells. (mean ± S.E.M. n = 3, **P < 0.01, ***P < 0.01, ****P < 0.0001)
