Ferroptosis in Glioblastoma and Neuroblastoma: Molecular Mechanisms and Novel Therapeutic Strategies

Abstract

Malignant neoplasms arising from the central nervous system (CNS), particularly glioblastoma (GBM) as well as neuroblastoma (NB), represent a formidable global health burden owing to their aggressive biological behavior and dismal clinical outcomes. Ferroptosis—an iron-dependent form of regulated cell death distinct from apoptosis, autophagy, and necrosis—has emerged as a critical regulatory nexus in the progression and therapeutic response of these malignancies. Characterized by iron-catalyzed lipid peroxidation, ferroptosis is tightly governed by the metabolic interplay among lipids, iron, and glutathione, profoundly influencing tumorigenesis, tumor progression, and therapeutic resistance. In this review, we systematically synthesize current knowledge on ferroptosis in GBM and NB, specifically contrasting how developmental origins and metabolic contexts shape their regulatory mechanisms. We further integrate recent advances in the diagnostic and therapeutic landscape of nervous system tumors, with a particular emphasis on ferroptosis-targeted strategies. Overall, this work aims to provide a conceptual framework linking ferroptosis regulation to tumor context, thereby offering mechanistic insights and future directions for the precision management of nervous system malignancies.