Glioblastoma multiforme (GBM) is known to be the most common and lethal malignant primary brain tumor.
Despite vigorous basic and clinical studies over the past decades, the prognosis of patients with GBM has remained dismal.
The fundamental problem with these malignancies occurs due to tumor cells’ highly infiltrative nature, precluding a
complete surgical resection, and a productive or acquired resistance to cytotoxic therapy. Recent studies demonstrated that
GBMs exhibited remarkable cellular heterogeneity and hierarchy containing self-renewing glioma stem cells (GSCs). The
malignant growth of GBM can be propagated and sustained by GSCs that are endowed with highly efficient clonogenic
and tumor initiation capacities. GSCs can be identified with technical support and are responsible for the invasive potential
and recurrence of GBMs. They share core signaling pathways with normal neural stem cells, but also display critical
distinctions that provide important clues for useful therapeutic targets. Therefore, targeting GSCs becomes priorities for
the development of novel therapeutic paradigms. Herein, we reviewed the existing and promising targeting therapies for
GSCs which could effectively inhibit the tumor invasion, proliferation and recurrence of GBMs. Significant features of
GSCs, such as invasive growth pattern, angiogenic potential, resistance to traditional therapy and differentiation, are important
therapeutic targets. More promising strategies should target GSCs themselves by taking advantages of highthroughput
technologies and dissecting the intrinsic molecular nature of GSCs. Novel chemical medicines targeting these
GSCs may represent one of the most important directions. Hopefully, this could shed a light on the path we are going to.
Keywords: Glioblastoma multiforme, glioma stem cells, antiangiogenisis, gene therapy, immunotherapy, viral therapy, cancer
stem cell, temozolomide, MGMT, CD133
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