Cell reports · 2025
Carvedilol sensitizes chemotherapy by targeting STING to boost anti-tumor immunity.
СтатьяНазвание и аннотация: Перевод в очереди
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Dang Yifang, Ma Mingtong, Wang Yan, Zhao Mengmeng, Cao Yajuan, Su Hang, Liu Tianhao, Zheng Mengge, Gao Jiani, Wu Xiangyang, Xu Junfang, Chen Li, Xi Jianzhong Jeff, Fei Yiyan, Liu Haipeng
Аннотация
The stimulator of interferon genes (STING)-mediated type I interferon (IFN) response is critical for mounting anti-tumor immunity and sensitizing chemotherapy by remodeling the tumor immune microenvironment. However, no clinically available drugs have been applied for STING activation. Based on high-throughput screening of small-molecule microarrays, we found that carvedilol, an adrenergic receptor blocker used to treat essential hypertension and symptomatic heart failure, is a STING activator. Mechanistically, carvedilol interacts with STING at threonine 263 and enhances its dimerization. Importantly, carvedilol enhances the therapeutic effect of etoposide in both the allografted tumor model and patient-derived tumor-like cell clusters (PTCs) by promoting etoposide-induced STING activation. Our findings identify carvedilol as a STING activator and provide a theoretical basis for combining carvedilol and etoposide in cancer therapy.