BRD4 inhibition sensitizes aggressive non-Hodgkin lymphomas to PI3Kδ inhibitors by suppressing PI3K reactivation and c-MYC expression.

ABSTRACT: Targeting phosphatidylinositol 3-kinase δ (PI3Kδ) is an important therapeutic strategy for indolent non-Hodgkin lymphomas (NHLs). However, we previously observed reactivation of phosphatidylinositol 3-kinase (PI3K) pathways in aggressive NHL cell lines following continuous exposure to PI3Kδ inhibitors (PI3Kδi), which limited their efficacy and suggests that more studies should be focused on this reactivation to improve current PI3Kδi-based treatments. Herein we conducted a drug synergy screening that combined a marketed PI3Kδi, idelalisib, with 14 well-characterized epigenetic drugs across several types of aggressive NHL cell lines. We identified BRD4 inhibitors (BRD4i) as potent partners that, in combination with idelalisib, were capable of synergistically exerting anti-proliferative acti

SUBMITTER: Zuo W 

PROVIDER: S-EPMC7840716 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature