Abstract
Glioblastoma multiforme (GBM) is the most highly invasive and malignant primary brain tumor in humans with median survival after diagnosis as low as 12-15 months. The poor prognosis of GBM is attributable to its resistance to current therapeutic approaches, consisting of maximal debulking surgery, chemotherapy with temozolomide, and radiotherapy. Amongst the heterogeneous population of tumor cells found in GBM, a self-renewing and proliferating cell type known as glioma stem-like cells (GSC) has been identified as a potential source for glioma therapy resistance. It has been well documented that current therapies fail to effectively eliminate GSC from the tumor population. This contributes to the virtually inevitable tumor recurrence in GBM patients following treatment. Therefore, GSC provide a particularly attractive target for the development of future therapies. This review highlights several proposed mechanisms behind therapy resistant glioma cells including DNA repair mechanisms, cell cycle checkpoints, drug efflux processes, and the role of the tumor microenvironment. Furthermore, several therapeutic strategies to target genes or pathways specific to GSC survival and proliferation will be discussed.
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