Resistance to BET inhibitors in lung adenocarcinoma is mediated by casein kinase phosphorylation of BRD4.

ABSTRACT: Targeting the epigenome to modulate gene expression programs driving cancer development has emerged as an exciting avenue for therapeutic intervention. Pharmacological inhibition of the bromodomain and extraterminal (BET) family of chromatin adapter proteins has proven effective in this regard, suppressing growth of diverse cancer types mainly through downregulation of the c-MYC oncogene, and its downstream transcriptional program. While initially effective, resistance to BET inhibitors (BETi) typically occurs through mechanisms that reactivate MYC expression. We have previously shown that lung adenocarcinoma (LAC) is inhibited by JQ1 through suppression of FOSL1, suggesting that the epigenetic landscape of tumor cells from different origins and differentiation states influences BETi respo

SUBMITTER: Calder J 

PROVIDER: S-EPMC7955060 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature