Redox biology of regulated cell death in cancer: A focus on necroptosis and ferroptosis

Abstract

Redox changes and generation of reactive oxygen species (ROS) are part of normal cell metabolism. While low ROS levels are implicated in cellular signaling pathways necessary for survival, higher levels play major roles in cancer development as well as cell death signaling and execution. A role for redox changes in apoptosis has been long established; however, several new modalities of regulated cell death have been brought to light, for which the importance of ROS production as well as ROS source and targets are being actively investigated. In this review, we summarize recent findings on the role of ROS and redox changes in the activation and execution of two major forms of regulated cell death, necroptosis and ferroptosis. We also discuss the potential of using modulators of these two forms of cell death to exacerbate ROS as a promising anticancer therapy.

Keywords: Anticancer therapy; Cancer; Ferroptosis; Necroptosis; ROS; Redox changes; Regulated cell death.