Targeting Ferroptosis Pathways: A Novel Strategy for Cancer Therapy

Abstract

Ferroptosis is an iron-dependent nonapoptotic kind of regulated cell death resulting from the destruction of redox balance in the cytosol. Unlike apoptosis, ferroptosis is caused by an increase in intracellular iron and lipid peroxides that causes significant damage to the membrane lipid bilayer and mitochondria leading to cell death. Increased iron level in the cell promotes ROS production. Ferroptosis inducer molecules increase ROS production and inhibit the antioxidant defence mechanism to facilitate ferroptosis in cancer cells. Inhibition of GPX4, redox-active iron availability, and lipid peroxidation are major contributors to ferroptosis. Ferroptosis is involved in many diseases like heart disease, neurodegenerative disease, and cancer. Ferroptosis induction recently emerged as an attractive strategy for cancer therapy. In this review, we discuss the regulatory mechanism of ferroptosis, its different hallmarks, including genetic and metabolic regulators and inducers that promote ferroptosis in the cancer cells. Finally, the latest progress and development in ferroptosis research in different cancers focusing on proposing a novel strategy in cancer therapy are discussed.

Keywords: Ferroptosis; cancer; hallmarks; inducer; redox imbalance; regulated cell death.