BET Inhibitors Target the SCLC-N Subtype of Small-Cell Lung Cancer by Blocking NEUROD1 Transactivation.

ABSTRACT: Small-cell lung cancer (SCLC) is a recalcitrant malignancy that urgently needs new therapies. Four master transcription factors (ASCL1, NEUROD1, POU2F3, and YAP1) have been identified in SCLC, and each defines the transcriptome landscape of one molecular subtype. However, these master transcription factors have not been found directly druggable. We hypothesized that blocking their transcriptional coactivator(s) could provide an alternative approach to target these master transcription factors. Here, we identify that BET proteins physically interact with NEUROD1 and function as transcriptional coactivators. Using CRISPR knockout and ChIP-seq, we demonstrate that NEUROD1 plays a critical role in defining the landscapes of BET proteins in the SCLC genome. Blocking BET proteins by inhibitors l

SUBMITTER: Chen H 

PROVIDER: S-EPMC9898120 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature