Dysregulated Signaling Pathways in Glioblastoma Cancer Stem-Like Cells: Potential Targets for Therapeutic Intervention

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive form of brain cancer. Despite advances in current therapeutic procedures including surgery, chemotherapy and radiation, there have been no significant improvements in patient survival. GBM tumors are highly heterogeneous and it is believed that a small proportion of the tumor mass is comprised of cancer stem-like cells (CSCs). The CSCs behave much like neural stem cells in that they can self-renew and undergo differentiation; however, their high tumor-initiating capacity and therapeutic resistance apparently drive tumorigenesis. Recent evidence depicts the involvement and crosstalk of several different signaling pathways in the regulation and progression of GBM. In this review, we discuss the PI3K-Akt, mTOR, Notch and JAK-STAT signaling pathways that often crosstalk to maintain GBM CSC survival. Furthermore, we discuss the potential role of epigenetic regulation of the CSCs. We believe that a thorough understanding of the signaling pathways that regulate GBM CSCs, and further molecular characterization of the GBM tumors, will lead to the development of more efficient therapies.