Degradation of BRD4 - a promising treatment approach not only for hematologic but also for solid cancer.
Karin Bauer, Anna S. Berghoff, Matthias Preusser, Gerwin Heller, Christoph Zielinski, Peter Valent, Thomas W. Grunt
Abstract
0.5-5 µM). Interestingly, when combined with commonly used cytotoxic therapeutics, dBET6 was found to promote anti-neoplastic effects and to counteract chemoresistance in most cancer cell lines. Moreover, JQ1 and both BET degraders strongly downregulated baseline and interferon-gamma induced expression of the immune checkpoint molecule PD-L1 in all cancer cell lines. Together, our data suggest that dBET6 outperforms first-generation BRD4 targeting drugs like dBET1 and JQ1, and decreases chemoresistance and immune resistance of cancer.
Topics & Concepts
BRD4BromodomainCancer researchOncogeneCancerImmune checkpointMelanomaBET inhibitorDownregulation and upregulationProstate cancerEpigeneticsBiologyCell cycleChemistryMedicineImmunotherapyGeneInternal medicineBiochemistryProtein Degradation and InhibitorsUbiquitin and proteasome pathwaysHistone Deacetylase Inhibitors Research