The Role of Ferroptosis in Cancer Development and Treatment Response

Abstract

Ferroptosis is a process driven by accumulated iron-dependent lipid ROS that leads to cell death, which is a distinct regulated cell death comparing to other cell death. The lethal metabolic imbalance resulted from GSH depletion or inactivation of glutathione peroxidase 4 is the executor of ferroptosis within the cancer cell. Small molecules-induced ferroptosis has a strong inhibition of tumor growth and enhances the sensitivity of chemotherapeutic drugs, especially in the condition of drug resistance. These evidences have highlighted the importance of ferroptosis in cancer therapeutics, but the roles of ferroptosis in tumorigenesis and development remain unclear. This article provides an overview of the mechanisms of ferroptosis, highlights the role of ferroptosis in cancer and discusses strategies for therapeutic modulation.

Keywords: cancer therapeutics; ferroptosis; iron metabolism; lipid ROS; tumorigenesis.

FIGURE 1

Mechanism of ferroptotic cell death. Ferroptosis is initiated by the inhibition of system Xc^- or GPX4 activity, which ultimately leads to cell death. Lipid ROS maybe responsible for the ferroptotic process. On the one hand, the peroxidation of PUFAs is considered to be an important contributor. On the other hand, excess irons are the basis for ferroptosis execution.