Genetic Profiles of Ferroptosis in Malignant Brain Tumors and Off-Target Effects of Ferroptosis Induction

Abstract

Glioblastoma represents the most devastating form of human brain cancer, associated with a very poor survival rate of patients. Unfortunately, treatment options are currently limited and the gold standard pharmacological treatment with the chemotherapeutic drug temozolomide only slightly increases the survival rate. Experimental studies have shown that the efficiency of temozolomide can be improved by inducing ferroptosis – a recently discovered form of cell death, which is different from apoptosis, necrosis, or necroptosis and, which is characterized by lipid peroxidation and reactive oxygen species accumulation. Ferroptosis can also be activated to improve treatment of malignant stages of neuroblastoma, meningioma, and glioma. Due to their role in cancer treatment, ferroptosis-gene signatures have recently been evaluated for their ability to predict survival of patients. Despite positive effects during chemotherapy, the drugs used to induce ferroptosis – such as erastin and sorafenib – as well as genetic manipulation of key players in ferroptosis – such as the cystine-glutamate exchanger xCT and the glutathione peroxidase GPx4 – also impact neuronal function and cognitive capabilities. In this review, we give an update on ferroptosis in different brain tumors and summarize the impact of ferroptosis on healthy tissues.