In this review, we will discuss ways to identify GSCs, their interactions with tumor microenvironment, and therapeutic advances to target GSCs. Emerging research suggest that the failure to target glioma stem cells (GSCs) rather than the inability to debulk tumors through surgical resection, radiation and chemotherapy, explain the poor survival of glioma patients ( Huse & Holland, 2010). Recent advances highlight the cellular heterogeneity in gliomas, the influence of the tumor microenvironment, and that treatment-resistant tumor cells display a high degree of stemness. Here, we will present recent experimental advances on the understanding of why humans are diagnosed with a certain type of glioma and where it came from. Recent molecular profiling of grade IV glioblastoma (GBM) exemplifies that subsets of tumors in children, young adults, and adolescents, that are indistinguishable by histology, can be segregated based on genetic alterations, broad-scale gene expression, and methylation patterns. Based on histological appearance, gliomas of most grades and types are found in children and adults. Classification by the World Health Organization (WHO) distinguishes malignancy by grade (I-IV). Gliomas can grossly be divided into astrocytic, oligodendrocytic, and ependymal phenotypes. We propose that more in-depth studies of OPC biology will inform novel preventive measures and therapeutic interventions to reverse the fatal outcome of most glioma patients. In this review, we present recent findings suggesting that the most wide-spread population of cycling cells in the pediatric and adult brain of mammalians, the oligodendrocyte progenitor cells (OPCs), represent a likely origin for large cohorts of gliomas. Modeling of glioma in mice has demonstrated that cells at various differentiation stages throughout glial and neuronal lineages have the potential to generate gliomas. Glial cells outnumber neurons by 10-fold in the human brain and are composed mainly of terminally differentiated cells and minor discrete precursor populations. The temporal and regional specificity of genetically distinct gliomas ( Sturm et al., 2012), argue that either several discrete populations of precursor cells may be vulnerable to transformation, or that multiple glioma subgroups share a common cell of origin. Recent advances in the molecular characterization of gliomas have defined subgroups of tumors that are genetically and epigenetically distinct ( Noushmehr et al., 2010 H.
Gliomas are the most common malignant primary brain tumor and associated with approximately 16,000 cancer-related deaths in United States per year ( Louis et al., 2007).