Article
BRD4 inhibition impairs DNA mismatch repair, induces mismatch repair mutation signatures and creates therapeutic vulnerability to immune checkpoint blockade in MMR-proficient tumors.
Journal for immunotherapy of cancer - 1 Apr 2023
Fu Yu, Yang Bin, Cui Yaoyuan, Hu Xingyuan, Li Xi, Lu Funian, Qin Tianyu, Zhang Li, Hu Zhe, Guo Ensong, Fan Junpeng, Xiao Rourou, Li Wenting, Qin Xu, Hu Dianxing, Peng Wenju, Liu Jingbo, Wang Beibei, Mills Gordon B, Chen Gang, Sun Chaoyang
Abstract excerpt
BACKGROUND: Mismatch repair deficiency (dMMR) is a well-recognized biomarker for response to immune checkpoint blockade (ICB). Strategies to convert MMR-proficient (pMMR) to dMMR phenotype with the goal of sensitizing tumors to ICB are highly sought. The combination of bromodomain containing 4 (BRD4) inhibition and ICB provides a promising antitumor effect. However, the mechanisms underlying remain unknown. Here,...
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