The antitumor activity of bromodomain inhibitors (BETi) has been demonstrated across numerous types of cancer. As such, these inhibitors are currently undergoing widespread clinical evaluation. However, predictive biomarkers allowing the stratification of tumors into responders and non-responders to BETi are lacking. Here, we show significant anti-proliferative effects of BETi in vitro and in vivo against aggressive SCCOHT1 ovarian cancer models lacking the SWI/SNF-related, SMARCA4 protein . Transcriptomic analysis revealed that exposure to BETi potently down-regulated the oncogenic receptor tyrosine kinase HER3 in SCCOHT1 but not in resistant OVCAR8 cells. Repression of this pathway is found to be an important determinant of response to BETi in cells harboring a loss of SMARCA4. Overall, we propose that BETi represent a rational therapeutic strategy in poor prognosis, SMARCA4 deficient cancers. SOURCE: Michael Witcher (michael.witcher@mcgill.ca) -  Lady Davis Institut

Pluto Bioinformatics

GSE102908: RNAseq data from SCCOHT1 and OVCAR8 ovarian cancer cells treated with BET inhibitors