Mechanisms regulating glioma invasion

Abstract

Glioblastoma (GBM) is the most aggressive, deadliest, and most common brain malignancy in adults. Despite the advances made in surgical techniques, radiotherapy and chemotherapy, the median survival for GBM patients has remained at a mere 14 months. GBM poses several unique challenges to currently available treatments for the disease. For example, GBM cells have the propensity to aggressively infiltrate/invade into the normal brain tissues and along the vascular tracks, which prevents complete resection of all malignant cells and limits the effect of localized radiotherapy while sparing normal tissue. Although anti-angiogenic treatment exerts anti-edematic effect in GBM, unfortunately, tumors progress with acquired increased invasiveness. Therefore, it is an important task to gain a deeper understanding of the intrinsic and post-treatment invasive phenotypes of GBM in hopes that the gained knowledge would lead to novel GBM treatments that are more effective and less toxic. This review will give an overview of some of the signaling pathways that have been shown to positively and negatively regulate GBM invasion, including, the PI3K/Akt, Wnt, sonic hedgehog-GLI1, and microRNAs. The review will also discuss several approaches to cancer therapies potentially altering GBM invasiveness.

Keywords: Glioblastoma; Hedgehog; Invasion; PI3K; Wnt.

Figure 1

Three major signaling pathways that have been reported to be involved in the invasiveness of GBM, namely the PI3K-Akt, Wnt and Shh-tGLI1 pathways.

Figure 2

Several miRNAs that have been shown to influence invasiveness in GBM and their targets. Green circles mark the microRNAs that act as tumor suppressors while the blue circle indicates the miRNA that acts as an onco-miR.