Ferroptosis in radiation-induced brain injury: roles and clinical implications

Abstract

Abstract Radiation-induced brain injury (RBI) presents a significant challenge for patients undergoing radiation therapy for head, neck, and intracranial tumors. This review aims to elucidate the role of ferroptosis in RBI and its therapeutic implications. Specifically, we explore how ferroptosis can enhance the sensitivity of tumor cells to radiation while also examining strategies to mitigate radiation-induced damage to normal brain tissues. By investigating the mechanisms through which radiation increases cellular reactive oxygen species (ROS) and initiates ferroptosis, we aim to develop targeted therapeutic strategies that maximize treatment efficacy and minimize neurotoxicity. The review highlights key regulatory factors in the ferroptosis pathway, including glutathione peroxidase 4 (GPX4), cystine/glutamate antiporter system Xc- (System Xc-), nuclear factor erythroid 2-related factor 2 (NRF2), Acyl-CoA synthetase long-chain family member 4 (ACSL4), and others, and their interactions in the context of RBI. Furthermore, we discuss the clinical implications of modulating ferroptosis in radiation therapy, emphasizing the potential for selective induction of ferroptosis in tumor cells and inhibition in healthy cells. The development of advanced diagnostic tools and therapeutic strategies targeting ferroptosis offers a promising avenue for enhancing the safety and efficacy of radiation therapy, underscoring the need for further research in this burgeoning field.

Keywords

• Ferroptosis
• Radiation-induced brain injury (RBI)
• Therapeutic strategies；Glutathione peroxidase 4 (GPX4)
• Reactive oxygen species (ROS)
• Radiation therapy