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11/10/2021

    Glioblastoma is the most common malignant primary brain tumor.



    Glioblastoma is the most common malignant primary brain tumor, with an incidence of 1–4 per 100,000 . The past decade has seen significant advances in our knowledge of glioblastoma pathophysiology. This includes detailed studies of genetics , epigenetics, and expression profiling  at the bulk- and single-cell level in large patient cohorts and in longitudinal studies , as well as barcoding studies in mouse models to understand glioblastoma cell hierarchies and plasticity . In addition, recent studies have demonstrated long-distance physical connections between glioblastoma cells and connections between glioblastoma cells and neighboring normal cells . These findings reinforce our understanding of glioblastoma as a highly heterogeneous cancer that exists as an almost organ-like structure distributed through much of the brain. In spite of these advances, glioblastoma remains an incurable disease with median survival after diagnosis of about 15 months. Frustratingly, therapies that have improved outcomes in other cancers have been ineffective in glioblastoma. Examples of this are the small molecule EGFR tyrosine kinase inhibitors, which enhance survival in lung cancer but are ineffective in glioblastoma  even though EGFR is amplified and mutated to a constitutively active form in many glioblastomas. Similarly, immune checkpoint inhibitors have also had success in other cancers, particularly melanoma, but again have been ineffective in glioblastoma.