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The emerging clinical potential of circulating extracellular vesicles for non-invasive glioma diagnosis and disease monitoring

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Abstract

Diffuse gliomas (grades II–IV) are amongst the most frequent and devastating primary brain tumours of adults. Currently, patients are monitored by clinical examination and radiographic imaging, which can be challenging to interpret and insensitive to early signs of treatment failure and tumour relapse. While brain biopsy and histologic analysis can evaluate disease progression, serial biopsies are invasive and impractical given the cumulative surgical risk, and may not capture the complete molecular landscape of an evolving tumour. The availability of a minimally invasive ‘liquid biopsy’ that could assess tumour activity and molecular phenotype in situ has the potential to greatly enhance patient care. Circulating extracellular vesicles (EVs) hold significant promise as robust disease-specific biomarkers accessible in the blood of patients with glioblastoma and other diffuse gliomas. EVs are membrane-bound nanoparticles shed from most if not all cells of the body, and carry DNA, RNA, protein, and lipids that reflect the identity and molecular state of their cell-of-origin. EVs can cross the blood–brain barrier and their release is upregulated in neoplasia. In this review, we describe the current knowledge of EV biology, the role of EVs in glioma biology and the current experience and challenges in profiling glioma-EVs from the circulation.

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Acknowledgements

All authors contributed to the manuscript preparation and approved the submission of the work presented here. We thank Brainstorm, a brain cancer research charity of RPA Hospital. S. Hallal is a recipient of an Australian Postgraduate Award and Australian Rotary Health postgraduate support.

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Author notes

  1. Kimberley L. Kaufman and Michael E. Buckland denotes co-authorship.

Authors and Affiliations

  1. Brainstorm Brain Cancer Research, Brain Tumour Research Laboratories, Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia

    Susannah Hallal, Kimberley L. Kaufman & Michael E. Buckland

  2. Discipline of Pathology, Sydney Medical School, University of Sydney, Camperdown, NSW, Australia

    Susannah Hallal, Saeideh Ebrahimkhani, Kimberley L. Kaufman & Michael E. Buckland

  3. Department of Neurosurgery, Chris O’Brien Lifehouse, Camperdown, NSW, Australia

    Brindha Shivalingam & Kimberley L. Kaufman

  4. Brain Tumour Research Laboratories, Brain and Mind Centre, Charles Perkins Centre, Bosch Institute and School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia

    Manuel B. Graeber

  5. Department of Neuropathology, Royal Prince Alfred Hospital, Brain and Mind Centre, Camperdown, NSW, Australia

    Saeideh Ebrahimkhani & Michael E. Buckland

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  1. Susannah Hallal
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  2. Saeideh Ebrahimkhani
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  4. Manuel B. Graeber
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  6. Michael E. Buckland
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Correspondence to Michael E. Buckland.

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Hallal, S., Ebrahimkhani, S., Shivalingam, B. et al. The emerging clinical potential of circulating extracellular vesicles for non-invasive glioma diagnosis and disease monitoring. Brain Tumor Pathol 36, 29–39 (2019). https://doi.org/10.1007/s10014-019-00335-0

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