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  • Review Article
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The biology of ependymomas and emerging novel therapies

Nature Reviews Cancer volume 22, pages 208–222 (2022)Cite this article

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Abstract

Ependymomas are rare central nervous system tumours that can arise in the brain’s supratentorial region or posterior fossa, or in the spinal cord. In 1924, Percival Bailey published the first comprehensive study of ependymomas. Since then, and especially over the past 10 years, our understanding of ependymomas has grown exponentially. In this Review, we discuss the evolution in knowledge regarding ependymoma subgroups and the resultant clinical implications. We also discuss key oncogenic and tumour suppressor signalling pathways that regulate tumour growth, the role of epigenetic dysregulation in the biology of ependymomas, and the various biological features of ependymoma tumorigenesis, including cell immortalization, stem cell-like properties, the tumour microenvironment and metastasis. We further review the limitations of current therapies such as relapse, radiation-induced cognitive deficits and chemotherapy resistance. Finally, we highlight next-generation therapies that are actively being explored, including tyrosine kinase inhibitors, telomerase inhibitors, anti-angiogenesis agents and immunotherapy.

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Fig. 1: Timeline of major discoveries in ependymoma.
Fig. 2: Molecular subgroups of ependymoma.
Fig. 3: Mechanisms of ependymoma tumorigenesis.

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Acknowledgements

The authors thank K. Antony Michealraj, Sachin Kumar and Polina Balin for their insightful feedback and suggestions.

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Authors and Affiliations

  1. MD Program, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Amr H. Saleh

  2. Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada

    Nardin Samuel, Kyle Juraschka, Michael D. Taylor & Michael G. Fehlings

  3. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada

    Mohammad H. Saleh

  4. Division of Neurosurgery, Department of Surgery, The Hospital for Sick Children, Toronto, ON, Canada

    Michael D. Taylor

  5. Division of Neurosurgery, University Health Network, Toronto Western Hospital, Toronto, ON, Canada

    Michael G. Fehlings

  6. Krembil Neuroscience Centre, University Health Network, Toronto, ON, Canada

    Michael G. Fehlings

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Contributions

A.H.S. conceived of the project, searched the literature, wrote the manuscript, and edited the manuscript. N.S., K.J., M.H.S., M.D.T. and M.G.F. reviewed and suggested edits to the manuscript. M.G.F. supervised the project. All authors reviewed the manuscript before submission.

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Correspondence to Michael G. Fehlings.

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Glossary

Ependymal cells

Ciliated epithelial glial cells located on the surface of brain and spinal cord ventricles.

Clear cell ependymoma

Rare ependymoma variant consisting mostly of cells that resemble oligodendrocytes (glial cells that produce myelin sheath).

Papillary ependymoma

Rare ependymoma variant consisting of cuboidal or columnar cells on top of finger-like stromal projections.

Tanycytic ependymoma

Rare ependymoma variant characterized by streams of hair-like cells.

Gliogenic progenitor cells

Progenitor cells that give rise to glial cells.

Roof-plate-like stem cells

Stem cells that have transcriptional similarity to the embryonic roof plate (the most dorsal structure of the neural tube).

Perinecrotic zones

Regions surrounding necrotic (dead) tissue.

Periventricular neural stem cells

(NSCs). Neural stem cells adjacent to the ventricles.

CpG island methylator phenotype

A state characterized by a high degree of DNA hypermethylation in CpG-rich promoters.

Telomere crisis

A state where DNA ends are substantially eroded leading to instability of chromosomes and, ultimately, cell death.

G-quadruplex secondary structures

Helical structures formed in guanine-rich nucleic acid sequences.

Neurospheres

Free-floating clusters of neural stem cells in cell culture.

Conformal radiation therapy

Form of radiation therapy wherein radiation beams closely fit the area of a tumour and match its shape.

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Saleh, A.H., Samuel, N., Juraschka, K. et al. The biology of ependymomas and emerging novel therapies. Nat Rev Cancer 22, 208–222 (2022). https://doi.org/10.1038/s41568-021-00433-2

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