The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway and ferroptosis have emerged as fundamental biological mechanisms that converge in regulating cellular homeostasis and disease pathogenesis. As a central component of innate immunity, the cGAS–STING axis detects cytosolic double-stranded DNA through cGAS-mediated synthesis of 2′3′-cyclic GMP–AMP, subsequently triggering STING-dependent activation of the TBK1–IRF3 and nuclear factor-κB signaling cascades. Ferroptosis, an iron-catalyzed form of regulated cell death, is characterized by the accumulation of phospholipid hydroperoxide due to compromised antioxidant activity and dysregulated iron metabolism. Accumulating evidence has revealed the intricate crosstalk between these pathways. This review systematically explores the structural and biochemical bases of both pathways, identifies key bridging molecules that mediate their interactions, and discusses therapeutic strategies targeting this crosstalk, particularly in cancer treatment.
Chen et al. (Fri,) studied this question.