Fig. 3: Transcriptomic profile of the capivasertib fulvestrant combination in parental versus palbociclib-resistant cells.

A Significant differentially expressed genes after combination treatment in parental T47D (z-scores of the mean expression). Each row represents a single gene. Columns represent relative expression for DMSO and combination treatment in parental, T47D RB−, T47D CDK6H cells. The number of genes that were significantly differentially expressed in PalboR lines as well as parental for combination vs DMSO are shown as the common genes below each column (the total number of DEG found in T47D RB− was 411 and for T47D CDK6H 484). B Significant differentially expressed genes after combination treatment in parental MCF7 are shown as z-scores, with each row representing a single gene with significant differential expression. Columns representing the changes in the same genes are shown for DMSO and capivasertib fulvestrant combination treatment comparing parental, MCF7 RB−, MCF7 PacqR cells. The number of genes that were also found to be significantly differentially expressed in PalboR lines are shown as the common genes below the relevant columns. MCF7 RB− had a total of 1531 DEG in comparison of capivasertib fulvestrant vs DMSO and MCF7 PacqR had a total 2300 DEG. C, D Overlap of downregulated genes enriched in pathways (blue) and upregulated genes enriched in pathways (red) in the comparison of combination treatment with DMSO in C T47D parental, T47D RB−, T47D CDK6H cells and D MCF7 parental, MCF7 RB− and MCF7 PacqR. E, F Pathway heatmaps representing the top 35 pathways ordered by combined log p-value across the groups. Pathways that are enriched in the downregulated DEG are shown in blue. All comparisons are combination vs DMSO (control) in each of E the three T47D cell lines and F the three MCF7 cell lines. Shade represents log p-value, the numbers to the right of the heatmap the total number of genes in the pathway and yellow numbers in boxes the DEG found in the pathway.