Recent advances in the molecular understanding of glioblastoma

Abstract

Glioblastoma is the most common and most aggressive primary brain tumor. Despite maximum treatment, patients only have a median survival time of 15 months, because of the tumor's resistance to current therapeutic approaches. Thus far, methylation of the O (6)-methylguanine-DNA methyltransferase (MGMT) promoter has been the only confirmed molecular predictive factor in glioblastoma. Novel "genome-wide" techniques have identified additional important molecular alterations as mutations in isocitrate dehydrogenase 1 (IDH1) and its prognostic importance. This review summarizes findings and techniques of genetic, epigenetic, transcriptional, and proteomic studies of glioblastoma. It provides the clinician with an up-to-date overview of current identified molecular alterations that should ultimately lead to new therapeutic targets and more individualized treatment approaches in glioblastoma.

Fig. 1

Simplified representation and integration of three commonly altered pathways involved in glioblastoma. Upper panel, the growth factor receptor/PI3K/AKT pathway. The lower panels depict the RB pathway (left) and the P53 pathway (right). Proteins that potentially act as tumor suppressors are indicated in green whereas oncoproteins are indicated in red. The growth factors binding to the receptors have been depicted in yellow

Fig. 2

Genetic pathways toward primary and secondary glioblastoma