Glioblastoma Multiforme

Glioblastoma Multiforme (GBM) is one of the most common and aggresive type of brain cancers. Ninetyseven percent of tumors belong to the 'classical' subtype, and carry extra copies of the epidermal growth factor receptor (EGFR) gene, and most have higher than normal expression of epidermal growth factor receptor (EGFR), whereas the gene TP53, which is often mutated in glioblastoma, is rarely mutated in this subtype. Downstream signaling of many RTKs, including EGFR, lead to activation of the PI3K/AKT/mTOR and RAS/RAF/MAPK secondary messenger systems. Dysregulation of these intracellular signaling pathways often occurs in GBM.PTEN is an endogenous inhibitor of PI3K and RAS, and it is often lost or mutated in GBM. Other signaling molecules in the PI3K and RAS pathways are also commonly mutated in GBM. These alterations further contribute to inappropriate P13K and RAS activity in GBM.