Glioblastoma is the most aggressive form of brain cancer in adults, characterized by rapid growth, invasive behavior and resistance to therapy. Standard treatment combines maximal surgical removal of the tumor with radiotherapy and chemotherapy, typically temozolomide. Despite this intensive approach, most tumors recur and median survival remains around 15 to 20 months, partly because infiltrating cancer cells are left behind in the brain.

Research shows that glioblastoma is highly heterogeneous. Individual tumors contain multiple subpopulations of cells with distinct genetic and molecular profiles, including so called glioma stem like cells that can drive recurrence. Common alterations affect pathways controlling cell growth, DNA repair and cell death. Identified changes include mutations in genes that regulate receptor tyrosine kinases, tumor suppressors and chromatin structure, as well as amplifications of growth factor receptors.

Single cell sequencing and advanced imaging are helping to map this complexity, revealing how tumor cells interact with surrounding brain tissue, blood vessels and immune cells. The tumor microenvironment, including hypoxic regions and supportive stromal and immune cells, promotes survival and therapy resistance.

New strategies aim to target these vulnerabilities. Approaches include drugs against specific signaling pathways, inhibitors of DNA repair to enhance radiotherapy, immunotherapies such as checkpoint inhibitors and engineered T cells, and treatments directed at glioma stem like cells. Researchers are also exploring personalized combinations based on each tumor’s molecular profile. Although no new standard therapy has yet transformed outcomes, this detailed understanding of glioblastoma biology is guiding more precise and potentially effective treatments.