Ferroptosis at the crossroads of tumor-host interactions, metastasis, and therapy response.

Abstract

Ferroptosis is a form of regulated cell death characterized by the accumulation of lipid peroxides in an iron-dependent manner. Ferroptotic cell death is modulated by many metabolic pathways, such as pathways governing the metabolism of sugars, lipids, amino acids, and iron, as well as mitochondrial activity and redox homeostasis. Tumor metastasis and therapy resistance are the main obstacles to curing cancers. Because tumor cells usually exhibit higher iron dependence than normal cells, they may be more susceptible to ferroptosis despite being resistant to other forms of cell death. Moreover, recent evidence has suggested that ferroptosis is involved in tumor-host interactions, modulates the tumor microenvironment, and serves as an antimetastatic mechanism. Thus, inducing ferroptosis in tumor cells has the potential to improve cancer treatment. Here, we review ferroptosis-regulating mechanisms and the roles of ferroptosis in malignant progression, including the tumor-host interactions, metastasis, and cancer therapy response.