Ferroptosis as a precise target for tumor-associated neutrophils: From molecular insights to targeted therapies

Ferroptosis is an iron-dependent form of regulated cell death characterized by the lethal accumulation of peroxidized lipids within cellular membranes and has emerged as a promising avenue in cancer therapy. Recent studies have indicated that pharmacologically induced ferroptosis can inhibit tumor progression; however, nonselective induction strategies often result in limited therapeutic efficacy because of a failure to account for the complex dynamics of the tumor microenvironment (TME). Neutrophils-the most abundant immune cells in humans-display remarkable phenotypic plasticity, adopting context-specific functions that can either promote or suppress tumor development. Their inherently high iron content renders them particularly vulnerable to ferroptosis, a process that is now recognized to contribute significantly to immunosuppression. This insight underscores the importance of incorporating neutrophil-related mechanisms into ferroptosis-based therapeutic strategies, both in terms of the tumor-promoting effects of neutrophil ferroptosis and their role in modulating tumor cell ferroptosis through iron metabolism reprogramming. This review highlights these dual mechanisms mediated by neutrophils and identifies potential therapeutic targets, offering new perspectives for enhancing ferroptosis-centered cancer treatments.