Targeting ferroptosis in lung cancer: emerging strategies and drug discovery opportunities

Lung cancer remains the leading cause of cancer-related mortality worldwide, with lung adenocarcinoma (LUAD) being its most prevalent histological subtype, which is plagued by severe drug resistance and dismal long-term survival. Current treatment approaches are often limited by drug resistance and metastasis. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, represents a promising novel therapeutic target to address these unmet clinical needs.

The authors of this narrative review synthesize the preclinical and translational evidence for ferroptosis-targeted lung cancer therapy and provide the reader with their expert perspectives on future development. Literature was retrieved from PubMed, Web of Science, Embase and China National Knowledge Infrastructure (CNKI) covering publications published between January 2018 and March 2026.

While ferroptosis induction effectively reverses therapeutic resistance in preclinical lung cancer models, its clinical translation is impeded by off-target toxicity, inconsistent subtype responses and the lack of validated predictive biomarkers. Ferroptosis agents will likely act as combinatorial adjuvants rather than monotherapies in the foreseeable future. Advancing subtype-selective compounds and multi-omics stratification signatures are essential to realize its clinical potential.