FERROPTOSIS IN THE PATHOGENESIS OF BRAIN TUMORS.

The field of research on ferroptosis has seen explosive growth in the past few years since the term was coined in 2012. This review highlights the current state of knowledge on the developmental mechanism of this unique mode of cell death, induced by iron-dependent phospholipid peroxidation and which is regulated by a variety of cellular metabolic events, including redox homeostasis. Among these factors, the xCT. system, an amino acid antiporter that supports the synthesis of glutathione (GSH) and oxidation protection. The risk of iron accumulation in neurons, astrocytes, oligodendrocytes, microglia, and Schwann cells and the development of oxidative stress is discussed. Ferroptosis triggers a cascade of events including activation of inflammation, oxidation of neurotransmitters, impaired neuronal communication, myelin sheath degeneration, astrocyte dysregulation, dementia, and cell death. On the other hand, the exceptional vulnerability to ferroptosis of cancer cells originating from the nervous tissue is estimated. Evidence is given for the initiation of ferroptosis in tumor cells as a factor in inhibiting the growth and death of these cells. Particular attention is paid to the pharmacological modulation of ferroptosis through its induction and inhibition for the treatment of drug-resistant cancers. The choice of targets for the induction of ferroptosis in cancer cells is discussed. Glutathione peroxidase 4 and xCT amino acid antiporter are recognized as the most preferred targets and the antitumor potential of their inhibition and side effects are being evaluated.