AIFM2 (Apoptosis Inducing Factor Mitochondria Associated 2)

Ferroptosis constitutes a promising therapeutic axis in SCLC. Integrating ferroptosis biomarkers into molecular stratification frameworks could refine patient selection and support precision oncology strategies, warranting further translational and clinical validation.

By reframing redox adaptation as a measurable, stratifiable, and targetable tumor state, this work provides a decision-oriented roadmap for state-aware precision oncology. Collectively, our framework supports a shift from mutation-centric treatment escalation toward clinical algorithms that anticipate and intercept redox-adapted therapeutic resistance, with direct implications for biomarker-enriched trials and adaptive treatment strategies in PDAC and beyond.

Integrating biochemical biomarkers, including insulin, IGF-1, leptin, adiponectin, hs-CRP, and estrogen metabolites, provides a systems-level framework for identifying individuals at elevated risk and guiding metabolic, nutritional, and lifestyle interventions. Overall, the biochemical architecture of EC underscores a central role for diet-modifiable metabolic and inflammatory pathways in carcinogenesis and survivorship, offering promising avenues for prevention and personalized metabolic health strategies.

We further identified ferroptosis suppressor protein 1 (FSP1) as a key downstream effector, which utilized ubiquinol (CoQH2) as a lipophilic radical-trapping antioxidant to block the accumulation of lipid peroxides to pro-ferroptotic levels. In summary, our findings demonstrated that ME1 promotes HCC progression by activating the NADPH-FSP1-CoQH2 axis and thereby inhibiting ferroptosis, suggesting a promising therapeutic strategy for HCC treatment.

This review introduces the systematic and mechanistic integration of the current knowledge base on the modulation of BC cells' ferroptosis susceptibility by epigenetic reprogramming across molecular subtypes. We critically assess the preclinical and translational evidence linking specific epigenetic regulators to ferroptosis evasion, identify emerging biomarkers predictive of ferroptosis vulnerability, and discuss the therapeutic potential of epigenetic-ferroptosis co-targeting strategies to restore ferroptosis sensitivity, circumvent drug resistance, and enhance survival outcomes in patients with refractory or metastatic BC.

Specifically, it elucidates how ferroptosis modulates immune cells such as CD8+ T cells and macrophages, reshaping the tumor immune microenvironment and offering new avenues for combination immunotherapy. We conclude by providing a roadmap for translating these insights into clinical practice, addressing current challenges, and outlining future directions for developing next-generation anticancer strategies.

Unlike other vitamins that inhibit ferroptosis by scavenging radicals, vitamin B2 supports ferroptosis resistance through FAD cofactor binding, ensuring proper FSP1 stability and function. This study provides a rich resource detailing mechanisms that regulate FSP1 abundance and highlights a novel connection between vitamin B2 metabolism and ferroptosis resistance, with implications for therapeutic strategies targeting FSP1 in cancer.

Furthermore, we show that the riboflavin antimetabolite roseoflavin markedly impairs FSP1 function and sensitizes cancer cells to ferroptosis. Our findings provide a rational strategy to modulate the FSP1-antioxidant recycling pathway and underscore the therapeutic potential of targeting riboflavin metabolism, with implications for understanding the interaction of nutrients, as well as their contributions to a cell's antioxidant capacity.

These findings not only elucidate the pharmacodynamic basis of HBE's anti-GC activity but also establish Arnicolide D as a promising dual-target ferroptosis inducer, providing a novel therapeutic strategy for GC treatment.

Accompanied by machine learning, the 10 biomolecules were ultimately identified as a potential biomarker panel for early diagnosis of HCC. It shows superior diagnostic efficacy (accuracy = 0.81, sensitivity = 0.74) over α-fetoprotein (AFP) (accuracy = 0.75, sensitivity = 0.45) for early HCC detection.