The most frequent tumor of the central nervous system in adults is Glioblastoma Multiforme (GBM), which represents the highest degree of malignancy of astrocyte lineage neoplasms. Standard treatment includes maximal resection, radiation, and chemotherapy as a first line therapy. The only approved targeted therapy for GBM is the antiangiogenic agent Bevacizumab, and due to the ultimate adaption to antiangiogenic therapy as well as the high grade of tumor heterogeneity, treatment of GBM remains clinically challenging. Analysis of the genomic landscape of GBM highlighted the most frequent genomic alterations, which affect MAPK, PI3K, p53 and/or RB signaling pathways. Mutations in the metabolic enzymes IDH1/2 occur frequently in low-grade gliomas, and although these are rarely mutated in primary GBM (aggressive form that arise de novo from astrocytes), IDH mutations are often found in secondary GBM (aggressive form that progress from lower-grade astrocytomas). IDH proteins mediate the conversion from Isocitrate to alpha Ketoglutarate (aKG), and mutant IDH further convert aKG to the oncometabolite 2HG, which in turn affects DNA methylation pattern. Identification of the IDH mutation and the partial evaluation of underlying molecular mechanism of their role in tumorigenesis created much excitement in the field of GBM. Potential targeted therapies for the mutant IDH proteins, inhibitors of 2HG or demethylating agents may proof beneficial in the treatment of secondary GBM.
For more info click here
TICC Faculty who are involved in Brain tumors research: