Brain tumor
Glioblastoma multiforme (GBM) is the most aggressive (grade IV) and most common form of a malignant brain tumor. Even when aggressive multimodality therapy consisting of radiotherapy, chemotherapy, and surgical excision is used, median survival is only 12–17 months. Standard therapy for glioblastoma multiforme consists of maximal surgical resection of the tumor, followed by radiotherapy between two and four weeks after the surgical procedure to remove the cancer, then by chemotherapy, such as temozolomide. Most patients with glioblastoma take a corticosteroid, typically dexamethasone, during their illness to relieve symptoms. Experimental treatments include targeted therapy, gamma knife radiosurgery, boron neutron capture therapy and gene therapy.
Glioblastoma
The "IDH1" gene encodes for the enzyme isocitrate dehydrogenase 1 and is frequently mutated in glioblastoma (primary GBM: 5%, secondary GBM >80%). By producing very high concentrations of the "oncometabolite" D-2-hydroxyglutarate and dysregulating the function of the wild-type IDH1-enzyme it induces profound changes to the metabolism of "IDH1"-mutated glioblastoma, compared with "IDH1" wild-type glioblastoma or healthy astrocytes. Among others, it increases the glioblastoma cells' dependence on glutamine or glutamate as an energy source. It has been hypothesized that "IDH1"-mutated glioblastoma are in a very high demand for glutamate and use this amino acid and neurotransmitter as a chemotactic signal. Since healthy astrocytes excrete glutamate, "IDH1"-mutated glioblastoma cells do not favor dense tumor structures but instead migrate, invade and disperse into healthy parts of the brain where glutamate concentrations are higher. This may explain the invasive behaviour of these "IDH1"-mutated glioblastoma.