Induction of ferroptosis in head and neck cancer: A novel bridgehead for fighting cancer resilience

Most head and neck cancers (HNCs) originate from mucosal epithelial cells and show epithelial traits. It often changes to a mesenchymal or poorly differentiated state as cancer progresses, leading to invasion, metastasis, and resistance to treatment. The loss of epithelial traits by the epithelial-mesenchymal transition may render resilient cancers vulnerable to a novel non-apoptotic regulated cell death ferroptosis by the iron-dependent accumulation of excessive lipid peroxidation. By regulating mitochondrial or iron metabolism, intracellular ferrous iron and lipid peroxidation accumulation can be boosted, making resistant cancer cells more susceptible to ferroptosis. This article discusses the potential effect of ferroptosis induction as a novel treatment for resilient HNCs.