cGAS-STING at the crossroads in cancer therapy

DNA is highly immunogenic, both exogenous and endogenous DNA can activate the pathogen-associated molecular pattern (PAMP) and danger-associated molecular pattern (DAMP), respectively, and hence activate the evolutionarily conserved cGAS-STING pathway for inflammatory responses. The cGAS-STING signaling pathway plays a very important role in the pathogenesis and progression of neoplastic diseases. For cancer therapy, there are some discrepancies on whether cGAS-STING should be inhibited or activated. Deregulated cGAS-STING signaling pathway might be the origin and pathogenesis of tumor, understanding and modulating cGAS-STING signaling holds great promise for cancer therapy. In this review article, we discuss the molecular mechanisms underlying cGAS–STING deregulation, highlighting the tumor inhibiting and promoting roles and challenges with cGAS–STING agonists in the context of cancer therapies.