Ferroptosis in Cancer and Beyond: Mechanisms, Biomarkers, and Interventions

Dear Colleagues,

Ferroptosis, a regulated, iron-dependent lipid peroxidation death program that has emerged as a bidirectional therapeutic lever in inducing ferroptosis to eliminate therapy-refractory cells and inhibiting ferroptosis to protect vulnerable tissues in acute or chronic injury. This Special Issue invites contributions spanning fundamental mechanisms (GPX4–GSH–System Xc⁻; FSP1/CoQ10 and GCH1/BH4 axes; ACSL4/LPCAT3-driven PUFA remodeling; iron handling and lipidomics) through translational and clinical science.

We especially welcome studies on the following topics: (i) Inducers in oncology, small molecules and drug repurposing that lower antioxidant capacity, disrupt cystine import, inhibit GPX4/FSP1, remodel lipids, or alter iron flux; determinants of sensitivity in tumor microenvironments (hypoxia, cytokines, stromal crosstalk); combinations with chemo/radiation/targeted and immunotherapies; biomarkers (lipid peroxidation adducts, oxidized phospholipids, imaging, genetic/chemical rescue). (ii) Inhibitors in non-malignant disease-tissue-protective strategies in neurodegeneration, stroke, cardiac/renal ischemia–reperfusion, infection/inflammation, and metabolic disorders, including iron chelation, radical-trapping antioxidants, and boosting endogenous ferroptosis suppressors.

Clinical and preclinical pipeline perspectives are encouraged: medicinal chemistry and delivery (including nanocarriers), PK/PD and target engagement, safety liabilities (off-target oxidative stress), patient stratification signatures, adaptive trial designs, and early clinical readouts. Method papers that standardize assays (lipid ROS quantification, iron speciation, genetic rescue) and establish reporting checklists to enhance rigor are prioritized. By bringing together inducers and inhibitors across malignant and non-malignant indications, this collection aims to map where ferroptosis therapeutics are most likely to succeed clinically and how to accelerate those paths.

Dr. Hareesh B. Nair
Guest Editor

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