Table summarizing STING activating therapies as anti-cancer treatments
| Category | Mechanism of action | Examples | Combination therapy with ICB |
|---|---|---|---|
| Direct STING agonist | Binds to STING to activate IFN/NF-κB signaling | cGAMP mimics Non-nucleotide STING agonist (e.g., MSA-2) Small molecules (e.g., MK-1454 and TAK-676) | cGAMP mimics and small molecules combined with anti-PD-1 in clinical trial |
| Indirect STING activators | Induce DNA damage/micronuclei to trigger STING activation | Chemotheraypy/radiotherapy PARP inhibitors (e.g., olaparib) Cell cycle inhibitors (e.g., palbociclib and paclitaxel) | PARP inhibitors and cell cycle inhibitors combined with anti-PD-1 in clinical trial |
| Nuclease inhibitors | Block DNA/cGAMP degradation to amplify STING signaling | TREX1 inhibitors ENPP1 inhibitors | Under investigation |
| Nanoparticle delivery | Enhances STING agonist delivery/tumor targeting | RGD@Ce6@MSA-2@Liposome ZIF-67 nanoparticles | Combined with anti-PD-1 in clinical trial |
cGAMP, cyclic GMP-AMP; DNA, deoxyribonucleic acid; ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase 1; ICB, immune checkpoint blockade; IFN, interferon; NF-κB, nuclear factor kappa B; PARP, poly(ADP-ribose) polymerase; PD-1, programed death-1; STING, stimulator of interferon genes; TREX1, three prime repair exonuclease 1.