Natural CDNs such as 3′,5′‐diguanylic acid (c‐di‐GMP) or monophosphate (2′3‐cGAMP or 3′3’‐cGAMP), showed anti‐tumor efficacy,[11, 55] however their intrinsic physiochemical characteristics like electronegativity and hydrophilicity as well as their susceptibility to enzymatic degradation by the phosphodiesterase ENPP1 limited their bioavailability within tumor tissues and narrowed the therapeutic window.[56] Hence, synthetic STING agonists, such as ADU‐S100 or BMS‐986301 are engineered for better stability and efficacy, thereby circumventing the disadvantages of natural CDNs. The gene discussed is STING1; the disease is neoplasm.