Ferroptosis induction via targeting metabolic alterations in head and neck cancer

Abstract

Ferroptosis is a newly regulated cell death induced by the accumulation of iron-mediated lipid peroxidation. The alteration of cancer metabolism may contribute to proliferation, metastasis, and treatment resistance in human cancers, implicating the sensitivity to ferroptosis induction. Altered metabolism in cancer cells regulates oxidative stresses and changes metabolism intermediates, contributing to their deregulated growth and proliferation. Cancer metabolic changes toward the elevation of cellular free iron and polyunsaturated fatty acids sensitize cancer cells to lipid peroxidation toxicity tightly linked to ferroptosis. The altered metabolism in cancers can be served as a promising target to reverse cancer therapeutic resistance by ferroptosis induction to selectively kill cancer cells while sparing normal cells. The role of mitochondria and lipid metabolism in inducing ferroptosis in head and neck cancer (HNC) has been elucidated in previous studies. Ferroptosis is receiving attention in cancer research as treating cancers altering cellular metabolism and refractory from conventional therapies. More in-depth studies are needed to develop highly therapeutic drugs and practical methods to induce ferroptosis in diverse cancer cells and tumor microenvironments effectively. Therefore, this review intends to understand the altered metabolism and find new therapeutic possibilities using ferroptosis in HNC.

Keywords: Ferroptosis; Head and neck cancer; Lipid peroxidation; Metabolism; Mitochondria.