Supplementary Figure S6 from Palazestrant (OP-1250), A Complete Estrogen Receptor Antagonist, Inhibits Wild-type and Mutant ER-positive Breast Cancer Models as Monotherapy and in Combination

Combination of OP-1250 with palbociclib or ribociclib enhances suppression of cell cycle-related gene expression. A, t-SNE plot of MCF7 xenograft samples from vehicle, low-dose OP-1250, and palbociclib monotherapy and combination treatment groups. B, C, Heatmap showing expression of genes associated with the E2 late gene signature and E2F gene signature of n = 3 MCF7 xenograft tumors from OP-1250 and palbociclib low dose monotherapy and combination therapy groups. Red indicates high expression relative to vehicle and blue indicates low expression. D, Comparison of log2-fold change values for 14 cell cycle-related genes between combination therapy (pink) and monotherapies (blue and purple for 1 mg/kg OP-1250 and 25 mg/kg palbociclib, respectively). Stacked bars represent the combined effect of the monotherapies according to the Bliss independence model. E, F, Heatmaps showing expression of genes associated with the G2/M and E2 late gene signatures of n = 3 MCF7 xenograft tumors from OP-1250 and ribociclib low dose monotherapy and combination therapy groups. Red indicates high expression relative to vehicle and blue indicates low expression. G, Venn diagram showing overlap in dysregulated genes relative to vehicle of 1 mg/kg OP-1250 + 25 mg/kg palbociclib and 1 mg/kg OP-1250 + 25 mg/kg ribociclib MCF7 xenograft tumors. H, Heatmap of genes associated with the kinetochore metaphase signaling pathway, the most enriched pathway (p-value 6.15×10-7) in 676 genes changed in both OP-1250 + CDK4/6 inhibitor treatment groups. Genes are color-coded by gene expression relative to vehicle, with red indicating high expression and blue indicating low expression. OP-1250 1 mg/kg treatment groups from two xenograft studies were averaged.