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Cancer stem cells and glioma

Nature Clinical Practice Neurology volume 4, pages 427–435 (2008)Cite this article

Abstract

Despite continued advances in surgical and medical therapies, the outcomes for patients diagnosed with glioblastoma multiforme remain dismal. Recent data suggest that progression of these brain tumors is driven by a small subpopulation of tumor cells, which are termed cancer stem cells (CSCs) because of their capability to self-renew, proliferate and give rise to progeny of multiple neuroepithelial lineages. According to the CSC hypothesis, current therapies that are extremely cytotoxic to the bulk of highly proliferative tumor cells fail to obliterate the relatively quiescent and resistant CSC compartment, thereby allowing these cells to survive and drive tumor recurrence. This Review summarizes current knowledge regarding neural stem cells in the normal adult brain and CSCs in glial tumors and discusses the implications of the CSC hypothesis for the development of future therapies for brain tumors.

Key Points

  • Despite continued advances in surgical and medical therapies, outcomes for patients diagnosed with glioblastoma multiforme (GBM) remain dismal

  • GBM progression is driven by a small subpopulation of tumor cells, termed cancer stem cells because of their capability to self-renew, proliferate and give rise to multiple neuroepithelial lineages

  • Neurogenesis continues throughout life in two germinal regions: the subventricular zone of the lateral ventricle and the dentate gyrus of the hippocampus

  • The cell of origin for GBM remains unclear, though there is evidence to support both NSC transformation and dedifferentiation of mature astrocytes in the genesis of gliomas

  • Brain tumor stem cells (BTSCs) are relatively resistant to current cytotoxic therapies; conventional therapies for high-grade gliomas might be more effective if combined with agents that increase the sensitivity of BTSCs to chemotherapy and radiation therapy

  • Novel therapies targeting BTSC differentiation are likely to be directed by our understanding of signaling pathways involved in normal NSC biology

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Figure 1: Neurospheres and the neurosphere assay.
Figure 2: The cancer stem cell hypothesis.

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Authors and Affiliations

  1. S Das is a Neurosurgical Resident and Research Fellow, M Srikanth is a Medical and Doctoral Student, and JA Kessler is Professor and Chairman of Neurology, all at the Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,

    Sunit Das, Maya Srikanth & John A Kessler

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  1. Sunit Das
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Correspondence to Sunit Das.

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Das, S., Srikanth, M. & Kessler, J. Cancer stem cells and glioma. Nat Rev Neurol 4, 427–435 (2008). https://doi.org/10.1038/ncpneuro0862

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