Abstract
During embryonic development, radial glial precursor cells give rise to neural lineages, and a small proportion persist in the adult mammalian brain to contribute to long-term neuroplasticity. Neural stem cells (NSCs) reside in two neurogenic niches of the adult brain, the hippocampus and the subventricular zone (SVZ). NSCs in the SVZ are endowed with the defining stem cell properties of self-renewal and multipotent differentiation, which are maintained by intrinsic cellular programs, and extrinsic cellular and niche-specific interactions. In glioblastoma, the most aggressive primary malignant brain cancer, a subpopulation of cells termed glioblastoma stem cells (GSCs) exhibit similar stem-like properties. While there is an extensive overlap between NSCs and GSCs in function, distinct genetic profiles, transcriptional programs, and external environmental cues influence their divergent behavior. This review highlights the similarities and differences between GSCs and SVZ NSCs in terms of their gene expression, regulatory molecular pathways, niche organization, metabolic programs, and current therapies designed to exploit these differences.
Highlights
Glioblastoma [GBM, International Classification of Diseases for Oncology (ICD-O) code 9440/3] is the most common and aggressive primary CNS malignancy in adults
The initial identification of a subpopulation of GBM cells with multilineage potency, increased self-renewal ability, proliferation, and migration, termed glioma stem cells (GSCs) [11,12,13] has provided correlative evidence for the possibility of GBMs arising from transformed neural stem cells (NSCs)
We describe the intrinsic and extrinsic regulations of subventricular zone (SVZ) NSCs and glioblastoma stem cells (GSCs) including molecular pathways, microenvironment, and metabolic activity to further evaluate how the differences can be exploited in the generation of targeted therapies for GBM
Summary
Glioblastoma [GBM, International Classification of Diseases for Oncology (ICD-O) code 9440/3] is the most common and aggressive primary CNS malignancy in adults. The short median survival of 9–18 months in patients with GBM has been attributed to the highly invasive nature of the disease with rapid cell infiltration, frequent relapses, and therapy resistance [1,2,3,4,5]. The current therapy for GBM, consisting of maximal surgical resection followed by radiation and temozolomide (TMZ), a cytotoxic chemotherapy [7], has yielded minimal survival benefit with a vast majority of GBM patients presenting with tumor recurrence. The addition of tumor-treating fields (TTFs) to the standard chemoradiotherapy regimen has extended survival of patients from 16 to 20.9 months [8]
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