Ferroptosis in Cancer: Mechanism and Therapeutic Potential

Abstract

Cancer drug resistance occurs when cancer cells evade cell death following treatment with chemotherapy, radiation therapy, and targeted therapies. This resistance is often linked to the reprogramming of programmed cell death (PCD) pathways, allowing cancer cells to survive drug-induced stress. However, certain anticancer therapies, when combined with specific agents or inhibitors, can induce ferroptosis-a form of cell death driven by iron-dependent lipid peroxidation. Currently, extensive preclinical and clinical research is underway to investigate the molecular, cellular, and tissue-specific mechanisms underlying ferroptosis, with the goal of identifying strategies to overcome drug resistance in cancers unresponsive to conventional PCD pathways. By harnessing ferroptosis, cancer cells can be compelled to undergo lipid peroxidation-induced death, potentially improving therapeutic outcomes in patients with cancer. This short review aims to enhance the understanding of ferroptosis inducers in cancer therapy and stimulate further research into ferroptosis-based approaches for more effective clinical cancer treatment.

Keywords: cell death; ferroptosis; iron; lipid peroxidation; oxidative stress; signaling.

Figure 1

A flow model showing the steps in ferroptosis involving various membrane and intracellular components, including transferrin receptors, glutamine-cystine antiporter (Xc), LOX, GPX, GSH, iron, and lipid peroxides [83].

Figure 2

A summary of the various molecular mechanisms of ferroptosis, with key genes involved in the induction of ferroptotic cell death in cancer cells.

Figure 3

A summary of various types of ferroptosis and their key genes that contribute to ferroptosis cell death [121,122,123,124].