Reprogramming the chemical reactivity of iron in cancer stem cells

Abstract Cancer stem cells (CSCs) have been shown to be refractory to conventional therapeutic agents, can promote metastasis, and have been linked to cancer relapse. Salinomycin can selectively kill CSCs. We have shown that salinomycin derivatives accumulate in lysosomes and sequester iron in this organelle. As a result, accumulation of iron leads to the production of reactive oxygen species and lysosomal membrane permeabilization, which in turn promotes cell death by ferroptosis. These findings have revealed the prevalence of iron homeostasis in CSCs and paved the way toward the development of next-generation therapeutics.