Glioblastoma is the most aggressive and common malignant brain tumor in adults, characterized by rapid growth, infiltrative behavior and resistance to treatment. Standard care typically includes maximal safe surgical removal of the tumor, followed by radiotherapy and chemotherapy with temozolomide, yet median survival usually remains around 15 to 18 months.

Research shows that glioblastoma is highly heterogeneous at the genetic and cellular levels. Key pathways often altered include those controlling cell cycle, growth factor signaling and DNA repair. Mutations in genes such as EGFR, PTEN, TP53 and alterations in the PI3K and Rb pathways are frequent. This diversity within and between tumors complicates targeted therapy, as subpopulations of cells may escape treatment and drive recurrence.

Cancer stem like cells in glioblastoma appear capable of self renewal, resistance to radiation and chemotherapy, and tumor regrowth after therapy. They are maintained by specific signaling pathways and microenvironmental conditions, including interactions with blood vessels and immune cells.

Immunotherapy is a major focus, with strategies such as immune checkpoint inhibitors, therapeutic vaccines, oncolytic viruses and engineered T cells being tested. Results so far have been mixed, with some promising responses but many patients showing limited benefit, reflecting the tumor’s immunosuppressive environment.

Tumor treating fields, which use alternating electric fields applied through scalp electrodes, have been shown to modestly extend survival when added to standard therapy. Ongoing research is integrating molecular profiling, novel drugs, advanced radiotherapy, device based therapies and immunotherapies to personalize treatment and overcome resistance mechanisms.