Update on glioblastoma: Biology, clinical management and emerging therapeutic strategies (Review)

Glioblastoma, an isocitrate dehydrogenase (IDH)‑wildtype central nervous system (CNS) World Health Organization grade 4 diffuse astrocytic tumor, remains the most aggressive primary malignancy of the adult CNS, with persistently poor outcomes despite advances in multimodal therapy. The present narrative review summarizes current knowledge on the glioblastoma epidemiology, molecular classification, prognostic biomarkers, standard treatment strategies, mechanisms of treatment resistance and emerging therapeutic approaches. The current standard of care consists of maximal safe surgical resection followed by radiotherapy to a total dose of 60 Gy with concurrent and adjuvant temozolomide. This approach results in a median overall survival of ~12‑15 months, with <10% of patients surviving >5 years. Clinical outcomes are strongly influenced by molecular characteristics, particularly the IDH mutation status and O6‑methylguanine‑DNA methyltransferase promoter methylation. However, durable disease control remains uncommon due to multiple resistance mechanisms, including limited drug delivery across the blood‑brain barrier, enhanced DNA repair capacity, the persistence of glioblastoma stem‑like cells, profound immunosuppression within the tumor microenvironment, and extensive intratumoral heterogeneity with ongoing clonal evolution. Emerging therapeutic modalities, including tumor‑treating fields, laser interstitial thermal therapy, dendritic cell vaccination, chimeric antigen receptor T‑cell therapy and immune checkpoint inhibition, have demonstrated biological activity and modest clinical benefit in selected settings; however, they have not yet produced transformative improvements in survival. Overall, meaningful progress in the management of glioblastoma will likely depend on precision medicine approaches that integrate molecular profiling, rational multimodal treatment combinations, and improved strategies for drug delivery and immune modulation.