Prospects for developing glioblastoma therapy using redox-targeting drugs: A narrative literature review

Introduction. Glioblastoma is the most common primary malignant brain tumor in adults. Despite modern treatment approaches involving surgical tumor resection followed by radiation and chemotherapy, the disease is typically associated with an unfavorable prognosis with the median survival of patients after diagnosis of about 14.6 months. This is largely attributable to the high chemoresistance of glioblastoma to therapy, determined, among other reasons, by its resistance to oxidative stress. Objective. Generalization of data on redox-dependent mechanisms of glioblastoma chemoresistance, as well as an analysis of the prospects for using drugs that destabilize redox homeostasis in glioblastoma therapy. Discussion. In response to therapy, tumor cells activate antioxidant systems, thereby retaining the release of reactive oxygen species induced by chemotherapeutic agents, stabilizing intracellular redox homeostasis, and preventing the development of oxidative stress. In this regard, the use of compounds that enhance the generation of intracellular reactive oxygen species or suppress the activity of key components of antioxidant defense appears to be a promising approach for sensitizing tumors to therapy. A number of drugs based on such compounds, either as monotherapy or in combination with other approaches, have shown efficacy in preclinical trials and demonstrated effectiveness in treating patients with glioblastoma during clinical studies. Conclusions. The search for more selective inhibitors of antioxidant systems, optimization of their delivery to the tumor, and patient stratification based on molecular-genetic and biochemical markers of tumor redox homeostasis could increase the effectiveness of glioblastoma therapy.