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Mechanisms of Disease: the role of stem cells in the biology and treatment of gliomas

Nature Clinical Practice Oncology volume 5, pages 393–404 (2008)Cite this article

Abstract

The study of neural stem cell and progenitor cell biology has improved our understanding of the biology of brain tumors in a developmental context. Recent work has demonstrated that brain tumors may harbor small subpopulations of cells that share characteristics of neural stem cells. There is still an ongoing debate about the specific role of these stem-like cells in cancer initiation, development and progression. Nonetheless, the concept of cancer stem cells has offered a new paradigm to understand tumor biology and resistance to current treatment modalities. Molecular aberrations in these cancer stem cells might be crucial targets for therapeutic intervention, with the hope of achieving more durable clinical responses. Recent studies have demonstrated that endogenous and transplanted neural stem cells and progenitor cells show a marked tropism to brain tumors. Although the mechanisms that govern these processes are poorly understood, the use of neural stem cells and progenitor cells as delivery vehicles for molecules toxic to tumors offers a promising experimental treatment strategy. This Review summarizes recent advances in the basic understanding of neural stem cell and cancer stem cell biology and the progress towards translating these novel concepts into the clinic.

Key Points

  • Cancer stem cells can be found in malignant gliomas and could be responsible for tumor initiation, tumor progression and resistance to current treatment strategies

  • Understanding the behavior and signaling in normal neural stem cell and progenitor cells will provide essential clues about genetic or epigenetic alterations in cancer stem cells and will be essential to developing successful novel therapies

  • A better understanding of 'stem cell niches' in the adult brain will allow essential insights into tumor behavior and treatment resistance

  • The analysis of purified cancer stem and progenitor cell populations with the development of novel lineage markers are likely to have an important impact on tumor classification and the debate about the 'cell-of-origin' in gliomas

  • The use of transplanted or endogenous progenitor cell populations might offer a powerful tool for promising future therapies to target dispersed cancer cells

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Figure 1: Lineage and differentiation in the central nervous system.
Figure 2: Neural stem cells (NSCs) in the adult mammalian brain (SVZ, hippocampus).
Figure 3: Glioblastomas are classified into two subgroups based on the predominance of certain genetic alterations.
Figure 4: Models of gliomagenesis.
Figure 5: Personalized translational neuro-oncology platform to discover and individualize treatments for brain tumor patients.

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Acknowledgements

We gratefully acknowledge the support of the Leonard A Florence Family Research Fund (to SK), the Wilmot Cancer Foundation (to JD), and the National Institute of Health (NIH; RO1-NS44701 to JD). SK is the recipient of a Sontag Soundation Distinguished Scientist Award and an NIH K08 award.

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  1. J Dietrich is a Clinical Fellow in the Department of Neurology at Brigham and Women's Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA.,

    Jörg Dietrich

  2. J Imitola is an Instructor in the Department of Neurology at Brigham and Women's Hospital and affiliated faculty of the Harvard Stem Cell Institute, Harvard Medical School, and S Kesari is an Assistant Professor at Harvard Medical School, Boston, MA, USA.,

    Jaime Imitola & Santosh Kesari

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Dietrich, J., Imitola, J. & Kesari, S. Mechanisms of Disease: the role of stem cells in the biology and treatment of gliomas. Nat Rev Clin Oncol 5, 393–404 (2008). https://doi.org/10.1038/ncponc1132

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