m6A RNA regulation connects ferroptosis and immune remodeling to therapeutic adaptation in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) exhibits marked molecular, metabolic, and immune heterogeneity, and treatment pressure further reshapes these states during the development of resistance. N6-methyladenosine (m6A) modification provides a dynamic post-transcriptional layer that controls RNA stability, translation, degradation, and processing, thereby influencing pathways involved in ferroptosis and tumor–immune interactions. Ferroptotic susceptibility is likewise state dependent and reflects the balance among redox-active iron, membrane lipid composition, and partially compensatory antioxidant systems. Emerging evidence indicates that these processes converge in lung cancer: m6A-dependent RNA regulation can alter cystine metabolism, GPX4-centered and GPX4-independent defenses, iron handling, and lipid remodeling, while ferroptotic stress can reciprocally modify checkpoint signaling, myeloid and stromal states, and CD8⁺ T-cell function. Importantly, these effects are compartment specific, because ferroptosis in malignant cells may enhance tumor control whereas ferroptotic injury in immune cells can impair antitumor immunity. Most current studies establish pairwise relationships among m6A regulation, ferroptosis, and immune remodeling, although a smaller number directly connect all three processes within the same experimental context. This review integrates these mechanistic layers, distinguishes causal evidence from association-based signatures, and examines how genotype and treatment history shape their interaction. We further discuss emerging therapeutic opportunities and the methodological and biomarker advances required to translate this framework into state-specific and biomarker-guided treatment strategies for NSCLC.