Abstract
Activation of the cGAS-cGAMP-STING pathway is essential for sensing foreign DNA from pathogens or self-DNA from dying cancer cells. This pathway is critical for the innate immune response and directs the full efficacy of cancer therapeutics, including checkpoint and PARP inhibitors, radiotherapy, and CAR T-cells. Intense efforts have focused on triggering this pathway with cGAMP analogs, which are small-molecule activators of STING. However, recent reports show that STING is downregulated by promoter methylation in various cancers.
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