Mechanism of ferroptosis resistance in cancer cells

Abstract

Ferroptosis is an iron-dependent cell death characterized by increased intracellular lipid peroxidation. Inducing ferroptosis has shown significant potential in eliminating various malignancies. However, the effectiveness of ferroptosis-based treatments is hampered by the intrinsic or acquired resistance of some tumors. In this review, we delineate the known mechanisms that regulate ferroptosis sensitivity and summarize the therapeutic application of ferroptosis inducers in cancer. Additionally, we discuss the roles of diverse signaling pathways that contribute to ferroptosis resistance in cancer cells, including the glutathione (GSH) and coenzyme Q (CoQ) pathways, NFE2-like bZIP transcription factor 2 (NRF2) antioxidant response, and lipid and iron metabolism. This emerging knowledge may serve as a foundation for developing novel anticancer strategies to overcome ferroptosis resistance.