Activation of stimulator of interferon genes (STING) and inhibition of vascular endothelial growth factor receptor (VEGFR) by telatinib induce antitumor activity.

ABSTRACT: The cGAS-STING signaling pathway is a crucial innate immune pathway that senses cytosolic DNA. Pharmacological activation of the cGAS-STING pathway might be a promising strategy for cancer immunotherapy. Here, we report that the cGAS-STING pathway is a new target of telatinib, an orally available vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor that has been investigated in clinical trials. In this study, we demonstrated that telatinib induced innate immune responses in a STING-dependent manner. In addition, we determined the crystal structure of STING bound to a telatinib analog, revealing the molecular interactions underlying STING activation. Moreover, we showed that telatinib-mediated STING activation contributed to the antitumor effects in tumor-bearing mouse models. I

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12907715 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature