Therapeutic impact of BET inhibitor BI 894999 treatment: backtranslation from the clinic.

ABSTRACT:

Background

BET inhibitors have been tested in several clinical trials where, despite encouraging preclinical results, substantial clinical benefit in monotherapy remains limited. This work illustrates the translational challenges and reports new data around the novel BET inhibitor, BI 894999. At clinically achievable concentrations, mechanistic studies were carried out to study pathway modulation and rational drug combinations.

Methods

BRD-NUT fusions are oncogenic drivers in NUT carcinoma (NC). The effects of BI 894999 on proliferation, chromatin binding and pathway modulation were studied in NC in vitro. These studies were complemented by efficacy studies either as a single agent or in combination with the clinical p300/CBP inhibitor CCS1477.

Results

Based on the mo

SUBMITTER: Tontsch-Grunt U 

PROVIDER: S-EPMC9346113 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature