Carvedilol sensitizes chemotherapy by targeting STING to boost anti-tumor immunity
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.
Authors
- Yajuan Cao (ORCID: https://orcid.org/0000-0001-8685-5787)
- Jiani Gao (ORCID: https://orcid.org/0000-0003-1422-8180)
- Jianzhong Xi (ORCID: https://orcid.org/0000-0003-3015-8418)
- Yiyan Fei (ORCID: https://orcid.org/0000-0002-2413-130X)
- Xiangyang Wu (ORCID: https://orcid.org/0000-0002-0444-7120)
- Mingtong Ma
- Mengge Zheng
- Yifang Dang
- Tianhao Liu (ORCID: https://orcid.org/0000-0002-1991-5863)
- Yan Wang (ORCID: https://orcid.org/0009-0009-0733-1674)
- Li Chen (ORCID: https://orcid.org/0000-0002-5127-5878)
- Haipeng Liu (ORCID: https://orcid.org/0000-0002-3338-6291)
- Mengmeng Zhao (ORCID: https://orcid.org/0000-0002-9682-6450)
- Junfang Xu (ORCID: https://orcid.org/0000-0002-4150-7305)
- Hang Su (ORCID: https://orcid.org/0000-0003-0571-0864)
Institutions
- Tongji University (CN)
- Peking University (CN)
- Fudan University (CN)
- Soochow University (CN)
- Jinan Central Hospital (CN)
- Shanghai Pulmonary Hospital (CN)
- Shandong First Medical University (CN)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-04-17
- DOI
- https://doi.org/10.1016/j.celrep.2025.115572
- Citations
- 5
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 3.99