Glioblastoma: From Pathophysiology to Novel Therapeutic Approaches

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. Despite the current standard of care therapy, including maximal surgical resection, chemoradiation, and tumor-treating fields, prognosis remains poor. Therapeutic failure is driven by an immunosuppressive tumor microenvironment, poor drug penetration across the blood–brain barrier, and robust resistance mechanisms. Epigenetic alterations further compound treatment resistance by enhancing DNA repair and promoting survival pathways. Molecular profiling has identified key prognostic and predictive biomarkers. Gene expression analyses have delineated GBM subtypes, each with distinct molecular features and therapeutic vulnerabilities that hinder successful clinical translation. This review integrates the pathophysiological, diagnostic, and therapeutic landscape of GBM to inform of future strategies for improved patient outcomes.