2025 · Cellular and Molecular Life Sciences · Springer · added 2026-04-21
Ferroptosis is a regulated form of cell death characterized by iron-dependent lipid peroxidation. It plays a crucial role in various pathological conditions, including neurodegenerative diseases, canc Show more
Ferroptosis is a regulated form of cell death characterized by iron-dependent lipid peroxidation. It plays a crucial role in various pathological conditions, including neurodegenerative diseases, cancer, ischemia–reperfusion injury, and organ failure. This review systematically explores the key mechanisms underlying ferroptosis, including polyunsaturated fatty acidcontaining phospholipid (PUFA-PL) peroxidation, iron metabolism, and mitochondrial dysfunction. Additionally, we summarize major endogenous ferroptosis defense systems, including the SLC7A11-glutathione (GSH)-glutathione peroxidase Show less
Cancer remains a major global health burden, with rising incidence and mortality linked to aging populations
and increased exposure to genotoxic agents. Oxidative stress plays a critical role in cance Show more
Cancer remains a major global health burden, with rising incidence and mortality linked to aging populations
and increased exposure to genotoxic agents. Oxidative stress plays a critical role in cancer development, progression, and
resistance to therapy. The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1
(KEAP1)-antioxidant response element (ARE) signaling pathway is central to maintaining redox balance by regulating
the expression of antioxidant and detoxification genes. Under physiological conditions, this pathway protects cells
from oxidative damage, however, sustained activation of NRF2 in cancer, often due to mutations in KEAP1, supports
tumor cell survival, drug resistance, and metabolic reprogramming. Recent studies demonstrate that NRF2 enhances
glutathione (GSH) synthesis, induces detoxifying enzymes, and upregulates drug efflux transporters, collectively
contributing to resistance against chemotherapy and targeted therapies. The inhibition of NRF2 using small molecules
or dietary phytochemicals has shown promise in restoring drug sensitivity in preclinical cancer models. This review
highlights the dual role of NRF2 in redox regulation and cancer therapy, emphasizing its potential as a therapeutic
target. While targeting NRF2 offers a novel approach to overcoming treatment resistance, further research is needed
to enhance specificity and facilitate clinical translation. Show less
Ferroptosis, a regulated form of cell death, is intricately linked to iron‑dependent lipid peroxidation. Recent evidence strongly supports the induction of ferroptosis as a promising strategy for trea Show more
Ferroptosis, a regulated form of cell death, is intricately linked to iron‑dependent lipid peroxidation. Recent evidence strongly supports the induction of ferroptosis as a promising strategy for treating cancers resistant to conventional therapies. A key player in ferroptosis regulation is ferroptosis suppressor protein 1 (FSP1), which promotes cancer cell resistance by promoting the production of the antioxidant form of coenzyme Q10. Of note, FSP1 confers resistance to ferroptosis independently of the glutathione (GSH) and glutathione peroxidase‑4 pathway. Therefore, targeting FSP1 to weaken its inhibition of ferroptosis may be a viable strategy for treating refractory cancer. This review aims to clarify the molecular mechanisms underlying ferroptosis, the specific pathway by which FSP1 suppresses ferroptosis and the effect of FSP1 inhibitors on cancer cells. Show less