Abstract
Significance:
Ferroptosis, an iron- and lipid peroxidation-dependent mode of programmed cell death, is presently realized as a converging mediator that bridges redox imbalance and metabolic dysfunction. Differing from apoptosis and necroptosis, ferroptosis involves iron homeostasis, glutathione depletion, and redox lipid damage. Thus, it becomes the intersection of metabolic reprogramming and redox signaling. Ferroptosis is a double-edged metabolic vulnerability and adaptive resistance pathway in malignancy.
Recent Advances:
Oncogenic signaling cascades such as PI3K/Akt/mTOR and AMPK restructure glucose and lipid metabolism to regulate ferroptotic sensitivity, whereas cancer cells destabilize antioxidant defense pathways such as X
Critical Issues:
Despite rapid advancements, foundational challenges persist, including the identification of ferroptosis-specific biomarkers, tissue-specific thresholds, and mechanisms for neutralizing off-target toxicity.
Future Directions:
Recently developed technologies such as CRISPR-based functional genomics, metabolomics, and AI-powered modeling represent new-age tools in defining ferroptosis networks and precision therapeutics design. Integration of the regulation of normal physiological ferroptosis into cancer and diabetes therapy has the potential to redefine redox-targeted therapy and metabolic medicine. Antioxid. Redox Signal. 44, 676–711.
Keywords
Get full access to this article
View all access options for this article.
