Glioblastoma multiforme (GBM) is the most aggressive adult brain cancer, and treatment remains challenging. Standard therapy combines surgery, radiation, and temozolomide (TMZ) chemotherapy, sometimes with tumor-treating fields. A key factor is MGMT promoter methylation—tumors with methylation respond better to TMZ, improving survival from about 12 to nearly 15 months.
Genetic profiling, including TERT promoter mutations, EGFR amplification, and chromosome changes, helps tailor therapy. Combining radiation, TMZ, and lomustine can extend survival beyond 34 months, and drugs like regorafenib may benefit patients with recurrent disease. GBM’s resistance is due to multiple active growth pathways, often involving EGFR, PDGFRA, PI3K/AKT/mTOR, TP53, and CDKN2A. Targeted drugs and pathway inhibitors, including IDH-targeted therapy for specific subtypes, are under study.
New strategies focus on multi-targeted approaches or immune activation, such as checkpoint inhibitors, CAR T-cells, vaccines, PARP inhibitors, gene therapy, and focused ultrasound to improve drug delivery. These advances offer hope for more durable GBM treatments.