Abstract
Glioblastomas (GBMs) are the most aggressive primary brain tumors and are heterogeneous at the cellular level. Current therapeutic means are limited to a largely palliative role, with modest improvement in clinical response. The cellular and molecular heterogeneity of GBMs indicates that individual mechanisms are likely to exert different levels of influences on patient treatment response. Glioma-propagating cells (GPCs) which are purportedly enriched in tumor-initiating and sustaining potential are important because they mirror primary tumors at the phenotypic and molecular level. Moreover, they display long-term self-renewal capability, possibly accounting for the frequently observed tumor recurrence and re-growth. Hence, elucidation of GPC targets that confer therapeutic resistance is essential for effective treatment outcome. Here, we highlight several key intrinsic mechanisms that contribute to the perpetuation of GPCs, including the multi-drug resistant phenotype, DNA damage repair as well as key self-renewal signaling cascades. Another integral factor is the paracrine cues from the perivascular/hypoxic milieu. Targeting these multifaceted pathways might therefore sensitize GPCs to chemotherapeutic agents and lead to long-lasting therapies. In addition, we discuss how transcriptome analysis of GPCs derived from histologically similar yet molecularly distinct primary tumors can stratify patient subtypes, each bearing their own unique genetic and clinical profile. These findings highlight the clinical contribution of GPCs to disease progression and survival outcome. Identification of patient subtypes may account for the heterogeneity in treatment response and thus accelerate the development of personalized therapy that can induce sustained clinical outcome. The road ahead will likely be filled with obstacles but these emerging therapeutic paradigms promise new opportunities to patient cohorts lacking in effective treatment options.
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Acknowledgements
 The authors would like to acknowledge grant support to C. Tang (BMRC: 09/1/33/19/611) and Singapore Institute for Clinical Sciences (A*STAR) core funding to B.T. Ang.
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Koh, L.W.H., Toh, T.B., Tang, C., Ang, B.T. (2014). Glioma Propagating Cells Show Enhanced Chemoresistance and Radioresistance (an Update). In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 11. Stem Cells and Cancer Stem Cells, vol 11. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7329-5_7
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DOI: https://doi.org/10.1007/978-94-007-7329-5_7
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