CircRNA-mediated regulation of ferroptosis in cancer: mechanistic networks and therapeutic implications.

Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation. In cancer, metabolic reprogramming is characterized by enhanced iron uptake, altered lipid metabolism, and sustained oxidative stress, creating a paradoxical state that increases vulnerability to ferroptosis while simultaneously activating antioxidant defense systems to sustain survival. Therefore, identifying and characterizing key regulators of pro-ferroptotic and anti-ferroptotic pathways is essential for precise modulation of ferroptosis sensitivity in cancer therapy. Circular RNAs (circRNAs) have emerged as important regulators of the ferroptosis network. Recent evidence indicates that circRNAs coordinate iron metabolism, lipid remodeling, redox balance, and stress-responsive signaling, thereby influencing tumor progression, stemness maintenance, immune adaptation, and therapy resistance. This review summarizes circRNA-mediated regulation of ferroptosis and highlights its mechanistic significance and translational potential in cancer.