Figure 5.

Mechanistic pathways and regulatory targets of ferroptosis. Ferroptosis is a form of cell death induced by iron overload and the accumulation of lipid peroxides. The Fenton reaction generates hydroxyl radicals via the interaction of Fe²⁺ and H₂O₂, which subsequently react with lipids to create lipid radicals, initiating lipid peroxidation. When antioxidant defenses, including the Xc⁻ system/GSH/GPX4 and FSP1/CoQ10/NAD(P)H pathways are suppressed, cells lose the ability to effectively inhibit lipid peroxidation, resulting in excessive ROS generation and ultimately causing cell death. DAMPs released from dying cells, including SAPE-OOH, HMGB1, KRAS^G12D mutant protein, and 8-hydroxy-2’-deoxyguanosine, are capable of regulating TAM differentiation. Meanwhile, M1-type TAMs promote ferroptosis in tumor cells, whereas M2-type TAMs exert inhibitory effects. Oxidized Phospholipids (OXPLs), Phospholipid Hydroperoxides (PL-OOH).