BRD2 Upregulation as a Pan-Cancer Adaptive Resistance Mechanism to BET Inhibition.

ABSTRACT: Bromodomain and extraterminal motif (BET) inhibitors, such as JQ1, are promising cancer therapeutics that target epigenetic regulators, particularly BRD4. However, resistance to BET inhibitors (BETi) limits their clinical utility, necessitating a better understanding of adaptive mechanisms. We identified BRD2 upregulation as a conserved response to BET inhibition across multiple cancer types and hypothesized that BRD2 compensates for BRD4 loss, sustaining essential transcriptional programs upon treatment. Consistent with this, BRD2 knockdown sensitized cancer cells to BETi in vitro , and combining BRD2 depletion and JQ1 treatment significantly impaired tumor growth in vivo . At the chromatin level, BRD2 and BRD4 ChIP-seq analysis of pancreatic cancer cells showed consistent B

SUBMITTER: Archasappawat S 

PROVIDER: S-EPMC12424687 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature