Targeting ESR1 mutation-induced transcriptional addiction with BET inhibition

We investigated the therapeutic potential of BET inhibition to target ESR1 mutation-induced “transcriptional addiction” in ER-positive breast cancer. Our studies show that ESR1 mutant (Y537S and D538G) cells activate unique transcriptional programs that are targeted by OTX015, a BET inhibitor Overall design: We performed gene expression profiling analysis (using RNA-seq) of MCF7 WT, Y537S and D538G cells treated with vehicle, b-estradiol and/or OTX-015 in hormone-deprived conditions to define transcriptional changes.