Metabolic Reprogramming and Ferroptosis: Unlocking New Therapeutic Frontiers in Cancer and Diabetes - PubMed

8 days ago

Ferroptosis is an iron- and lipid peroxidation-dependent form of programmed cell death, linking redox imbalance and metabolic dysfunction.
Unlike apoptosis and necroptosis, ferroptosis involves iron homeostasis, glutathione depletion, and redox lipid damage, making it a key intersection of metabolic reprogramming and redox signaling.
Oncogenic pathways like PI3K/Akt/mTOR and AMPK regulate ferroptotic sensitivity by restructuring glucose and lipid metabolism, while cancer cells evade ferroptosis via antioxidant defense pathways like Xc--GSH-GPX4 and FSP1-CoQ10-NAD(P)H.
Pharmacological inducers such as erastin, RSL3, and sorafenib enhance antitumor effects and immune modulation by reversing oxidative imbalance.
In diabetes, ferroptosis contributes to β-cell deterioration, insulin resistance, and vascular injury, driven by hyperglycemia-induced oxidative stress and dysregulated GPX4.
Iron overload and mitochondrial dysfunction exacerbate ferroptotic injury in diabetic complications like cardiomyopathy, nephropathy, retinopathy, and foot ulcers.
Key challenges include identifying ferroptosis-specific biomarkers, tissue-specific thresholds, and mechanisms to mitigate off-target toxicity.
Emerging technologies like CRISPR, metabolomics, and AI-powered modeling offer new tools for understanding ferroptosis networks and designing precision therapeutics.
Integrating ferroptosis regulation into cancer and diabetes therapy could redefine redox-targeted treatments and metabolic medicine.

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