The BRD4 inhibitor JQ1 augments the antitumor efficacy of abemaciclib in preclinical models of gastric carcinoma.

ABSTRACT:

Background

Advanced gastric cancer (GC) is a lethal malignancy, harboring recurrent alterations in cell cycle pathway, especially the CDKN2A-CDK4/CDK6/CCND1 axis. However, monotherapy of CDK4/6 inhibitors has shown limited antitumor effects for GC, and combination treatments were urgently needed for CDK4/6 inhibitors.

Methods

Here, we performed a comprehensive analysis, including drug screening, pan-cancer genomic dependency analysis, and epigenetic sequencing to identify the candidate combination with CDK4/6 inhibitors. Mechanisms were investigated by bulk RNA-sequencing and experimental validation was conducted on diverse in vitro or in vivo preclinical GC models.

Results

We found that the BRD4 inhibitor JQ1 augments the antitumor efficacy of the CDK4/6 inhibitor ab

SUBMITTER: Feng M 

PROVIDER: S-EPMC9909925 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature