Ferroptosis in glioblastoma: Molecular determinants, immune crosstalk, and therapeutic opportunities.

Glioblastoma(GBM) is characterized by rapid recurrence and resistance to radiochemotherapy, highlighting the need for therapeutic vulnerabilities that extend beyond genetic subtypes. Ferroptosis, an iron-dependent form of lipid peroxidation-driven cell death, has emerged as a promising but complex vulnerability in GBM. In this review, we summarize how ferroptotic sensitivity is shaped by core iron-lipid-antioxidant machinery and by GBM-specific regulatory layers, including mitophagy, m6A-dependent GPX4 regulation, lipid metabolic remodeling, and DNA damage-associated stress responses. We further discuss how ferroptosis interacts with the GBM immune microenvironment, where it may either promote antitumor immunity or be exploited to induce immune-cell dysfunction. Finally, we evaluate therapeutic strategies that combine ferroptosis modulation with radiotherapy, temozolomide chemotherapy, immunotherapy, and nanomedicine-based delivery. We propose that ferroptosis-targeted strategies in GBM should be guided by tumor context, immune-cell preservation, and biomarker-based patient stratification.