The low-dose CHK1 inhibitor prexasertib triggers VDAC1 dephosphorylation to activate mtDNA-STING signaling and synergize immunotherapy

The low-dose CHK1 inhibitor prexasertib triggers VDAC1 dephosphorylation to activate mtDNA-STING signaling and synergize immunotherapy

Summary: CHK1 inhibitors exhibit dose-limiting toxicity despite potent tumor cytotoxicity in clinical trials. Here, we reveal that low-dose prexasertib induces mtDNA damage by impairing repair machinery, triggering cytosolic mtDNA release via VDAC1 to activate STING-mediated innate immunity. Mechani...

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Main Authors: Yu Fu, Xiaoyan Kang, Wenting Li, Zanhong Wang, Wanwan Luo, Bin Yang, Yaoyuan Cui, Funian Lu, Tianyu Qin, Xingyuan Hu, Jingjing Yin, Xi Li, Junpeng Fan, Beibei Wang, Gang Chen, Rourou Xiao, Zhiqiang Han, Ensong Guo, Xu Qin
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Cell Reports
Subjects:
CP: Cancer
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725003766
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http://www.sciencedirect.com/science/article/pii/S2211124725003766

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