Precision Targeting of Ferroptosis: From Molecular Defense Networks to Disease-Specific Translation

Ferroptosis is a type of regulated cell death driven by iron-dependent phospholipid peroxidation. A recent review by Zemnou and Ngakam comprehensively summarized the regulatory network of ferroptosis and its implications in cancer, neurodegenerative diseases, and drug development. This review illustrates that ferroptosis is not merely a consequence of increased reactive oxygen species but rather a failure to maintain homeostasis involving redox-active iron, oxidizable phospholipids, and compartmentalized antioxidant defenses. The context-dependent biology of ferroptosis underlies the complexity of its therapeutic modulation: inducing ferroptosis may eliminate therapy-resistant cancer cells, while inhibiting ferroptosis may protect vulnerable neurons in neurodegenerative diseases. However, clinical translation remains limited by the absence of validated biomarkers, insufficient pharmacological selectivity, and opposing responses among different cell populations. Future development should therefore move from nonspecific modulation toward disease-specific dependencies, cell-type-resolved biomarkers, and targeted, controllable therapeutic interventions.