2. Academic Validation
  3. Carvedilol sensitizes chemotherapy by targeting STING to boost anti-tumor immunity

Carvedilol sensitizes chemotherapy by targeting STING to boost anti-tumor immunity

  • Cell Rep. 2025 May 27;44(5):115572. doi: 10.1016/j.celrep.2025.115572.
Yifang Dang 1,  Mingtong Ma 2,  Yan Wang 3,  Mengmeng Zhao 4,  Yajuan Cao 5,  Hang Su 6,  Tianhao Liu 3,  Mengge Zheng 3,  Jiani Gao 6,  Xiangyang Wu 7,  Junfang Xu 8,  Li Chen 7,  Jianzhong Jeff Xi 9,  Yiyan Fei 10,  Haipeng Liu 11
Affiliations

Affiliations

  • 1 Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Department of Microbiology and Immunology, School of Medicine, Tongji University, Shanghai 200072, China; Central Laboratory, Taicang Hospital Affiliated to Soochow University, Taicang 215400, China.
  • 2 Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
  • 3 Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Department of Microbiology and Immunology, School of Medicine, Tongji University, Shanghai 200072, China.
  • 4 Research Center of Translational Medicine, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • 5 Department of Integrated Traditional Chinese and Western Medicine, Tongji University School of Medicine, Shanghai 200433, China.
  • 6 Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
  • 7 Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
  • 8 Clinical Translation Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
  • 9 State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.
  • 10 Department of Optical Science and Engineering, Shanghai Engineering Research Center of Ultra-Precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Fudan University, Shanghai 200433, China.
  • 11 Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Department of Microbiology and Immunology, School of Medicine, Tongji University, Shanghai 200072, China. Electronic address: haipengliu@tongji.edu.cn.
PMID: 40249703 DOI: 10.1016/j.celrep.2025.115572
Abstract

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.

Keywords

CP: Cancer; CP: Immunology; STING; carvedilol; combination therapy; etoposide; type I IFN response.

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