The cellular origin for malignant glioma and prospects for clinical advancements

Abstract

Glioma remains incurable despite great advancements in medicine. Targeting the cell of origin for gliomas could bring great hope for patients. However, as a collection of diverse diseases, each subtype of glioma could derive from a distinct cell of origin. To resolve such a complex problem, one must use multiple research approaches to gain deep insights. Here we review current evidence regarding the cell of origin from clinical observations, whole-genome molecular pathology and glioma animal models. We conclude that neural stem cells, glial progenitors (including oligodendrocyte progenitor cells) and astrocytes could all serve as cells of origin for gliomas, and that cells incurring initial mutations (cells of mutation) might not transform, while their progeny cells could instead transform and act as cells of origin. Further studies with multidisciplinary approaches are needed to link each subtype to a particular cell of origin, and to develop effective therapies that target the signaling network within these cells.

Keywords::

• animal model
• astrocyte
• cell of mutation
• cell of origin
• cell-targeted therapy
• malignant glioma
• molecular pathology
• neural stem cell
• oligodendrocyte progenitor cell
• tumor subtype

Acknowledgements

We thank Ben Barres for helpful discussions.

Financial & competing interests disclosure

H Zong would like to acknowledge grant support by National Cancer Institute (NIH/NCI) grant number R01CA136495 and the WM Keck Foundation. H Zong is a Pew Scholar in Biomedical Sciences, supported by The Pew Charitable Trusts. RGW Verhaak would like to acknowledge support by National Cancer Institute (NIH/NCI) grant number U24CA143883. P Canoll would like to acknowledge support by National Institute of Neurological Disease (NIH/NINDS) grant number R01NS066955. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the NIH.The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.