Oxidative Stress and Antioxidants in Glioblastoma: Mechanisms of Action, Therapeutic Effects and Future Directions

Glioblastoma (GB) is an aggressive and treatment-resistant primary brain tumor with a dismal prognosis. Increasing evidence implicates oxidative stress as a central driver of its pathogenesis, progression, and resistance to therapy. The dynamic interplay between oxidative stress and antioxidant mechanisms is fundamental to understanding GBM biology and shaping novel therapeutic approaches. This review synthesizes current knowledge on the multifaceted role of redox biology in glioblastoma, highlighting the molecular mechanisms through which oxidative stress influences tumor proliferation, survival, immune evasion, and metabolic adaptation. Particular focus is given to the tumor microenvironment, hypoxia-driven reactive oxygen species, redox-regulating enzymes, and the immunosuppressive conditions fostered by oxidative stress. Antioxidants, in this context, demonstrate a dual role: while they can mitigate oxidative damage, their effects on cancer cells and treatment outcomes vary depending on the therapeutic setting. We further examine emerging strategies that target oxidative pathways, including small-molecule inhibitors, redox-modulating agents, and combinatorial approaches with standard treatments, while also addressing the complexities posed by antioxidant interventions. Preclinical and clinical findings are reviewed to underscore both the opportunities and challenges of exploiting redox vulnerabilities in GB. Ultimately, a deeper understanding of oxidative stress dynamics and antioxidant regulation may guide the development of innovative therapies that overcome resistance and improve outcomes for patients facing this devastating malignancy.