Abstract
Malignant brain tumors are a heterogeneous group of diseases arising from different cell types that affect both adults and children. The high recurrence rate of malignant brain tumors typically is due to reappearance of focal masses, indicating that a sub population of tumor cells are insensitive to current therapies and may be responsible for reinitiating tumor growth. It is generally agreed that the resistant tumor cells are comprised of cancer stem cells or tumor-initiating cells. While brain tumor stem cells (BTSCs) were first isolated within the last decade, much of the early research has been focused on identifying the BTSC markers and therapeutic targets. The challenge however, is to translate this knowledge to therapeutics. In the current review, we survey the remedial strategies to target BTSCs, which includes diagnostic, pharmacologic, immunologic, viral, and post-transcriptional approaches.
Highlights
1.1 Introduction to brain tumor stem cells (BTSCs) TherapeuticsMalignant brain tumor is a leading cause of cancer-related death in children
Drugs preventing L-MYC (Li, Oganesyan et al 2016), HMGA-2 (Zhong, Liu et al 2016), fatty acid synthase (FASN) (Yasumoto, Miyazaki et al 2016), astrocyte elevated gene-1 (AEG-1) (Hu, Emdad et al 2016), and lysine demethylase KDM1A (Sareddy, Viswanadhapalli et al 2016) activity and promoting PAX6/DLX5 transcriptional activation of WNT signaling (Hu, Wang et al 2016) prevented glioma stem cell morphology and induced astrocytic differentiation. These preclinical studies suggest that eliminating the glioblastoma stem cell (GBSc) population and inducing astrocytic differentiation of the glioma cells may be a viable selective treatment strategy to explore for BTSCs, further testing is needed in an in vivo systems
Myxoma virus (MYXV), in combination with rapamycin has been successfully shown to promote anti-tumor activity of BTSCs in mice infected with glioblastoma multiformeted and reduce CD133 expressing stem cells (Zemp, Lun et al 2013)
Summary
Malignant brain tumor is a leading cause of cancer-related death in children. In 2004, an estimated 7.2 per 100,000 people in the US developed malignant brain tumors, with a 5-year survival rate of only 28% (Porter, McCarthy et al 2010). It is generally agreed that a high rate of recurrence in brain tumor is due to the resistance of a sub-population of cancer stem cells (CSCs) or tumor-initiating cells (Clarke, Dick et al 2006). A retrospective analysis found that targeting the BTSC niche (distinct from the neural stem cell population) – with radiotherapy - led to a significantly decreased risk of the disease progression and dose-dependent improvement in patient survival (Evers, Lee et al 2010). These recent studies suggest that BTSCs may have clinical relevance in malignant brain tumors. Vol 7, No 1; 2018 recent and ongoing therapeutic approaches and strategies to target BTSCs
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