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

TL;DR

This paper reviews how ferroptosis, a type of cell death, influences brain and nerve tumors and explores new treatment strategies.

Contribution

The paper provides a systematic synthesis of ferroptosis mechanisms and therapeutic strategies in glioblastoma and neuroblastoma.

Findings

Ferroptosis is regulated by lipid peroxidation, iron, and glutathione metabolism in CNS tumors.

Ferroptosis regulation varies between glioblastoma and neuroblastoma due to distinct developmental and metabolic contexts.

Targeting ferroptosis offers new diagnostic and therapeutic opportunities for nervous system malignancies.

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.

Figures