Nrf2--a hidden bridge linking cancer stem cells to ferroptosis

Cancer stem cells (CSCs), a small population of stem cells existing in cancer cells, are considered as the "culprits" of tumor recurrence, metastasis, and drug resistance. Ferroptosis is a promising new lead in anti-cancer therapy. Because of unique metabolic characteristics, CSCs’ growth is more dependent on the iron and lipid than ordinary cancer cells. When the metabolism of iron/lipid is disordered, that is, imbalanced redox homeostasis, CSCs are more susceptible to ferroptosis. The expression of Nuclear factor E2-related factor 2 (Nrf2), a molecule playing a major regulatory role in redox homeostasis, determines whether the cells are under oxidative stress and ferroptosis occurs. Nrf2 expression level is higher in CSCs, indicating stronger dependence on Nrf2. Here we expound the unique biological and metabolic characteristics of CSCs, explore the mechanism of inducing ferroptosis by targeting Nrf2, thus providing promising new targets for eliminating aggressive tumors and achieving the goal of curing tumors.