Self-renewal signaling pathways and differentiation therapies of glioblastoma stem cells (Review)

Glioblastoma multiforme (GBM) is a primary brain tumor with a high mortality rate and a median survival time of similar to 14 months from the initial diagnosis. Although progress has been made in the currently available therapies, the treatment of GBM remains palliative. GBM contains subsets of GBM stem cells (GSCs) that share numerous neural stem/progenitor cell characteristics, such as expression of stem cell markers, self-renewal and multi-lineage differentiation capacity, thus contributing to the heterogeneity and complexity of these tumors. GSCs are potentially associated with tumor initiation and they are considered as the driving force behind tumor formation, as they possess tumor-propagating potential and exhibit preferential resistance to radiotherapy and chemotherapy. Targeting self-renewal signaling pathways in cancer stem cells may effectively reduce tumor recurrence and significantly improve prognosis. The aim of the present review was to summarize the current knowledge on the self-renewal signaling pathways of GSCs and discuss potential future targeting strategies for the design of differentiation therapies.