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Topic: Brain tumor cell invasion and metastasis: anatomical,
biological and clinical considerations

Targeting cerebrospinal fluid for discovery of brain cancer biomarkers

Tarek Shalaby, Federica Achini, Michael A. Grotzer
Department of Oncology, University Children’s Hospital Zürich, Steinwiesstrasse 75, CH-8032 Zürich, Switzerland.
Correspondence to: Dr. Tarek Shalaby, Department of Oncology, University Children’s Hospital Zürich, Steinwiesstrasse 75, CH-8032 Zürich, Switzerland.
E-mail: tarek.shalaby@kispi.uzh.ch

Dr. Shalaby obtained his MD-PhD degree in molecular and cell biology at the University of Bern,
Switzerland. He was then a postdoc at neuro-oncology at University Children’s Hospital, Zurich. He is
now a senior scientist at the oncology department, University Children’s Hospital, Zurich and the Editor-
in-Chief of the Journal of Unexplored Cancer Data.

A B S T R AC T
Central nervous system (CNS) cancer is a devastating illness with unmet therapeutic needs. Establishing biomarkers that have the
potential to guide accurate CNS cancer diagnosis or are helpful in predicting disease progression or therapy response is of great
interest. Cerebrospinal fluid (CSF) has been extensively targeted for the detection of molecules that might be useful markers for
cancer detection. However, so far very few of such markers have found a standardized routine clinical application. This review
examines the current scientific knowledge about the biochemical elements in the CSF that have been reported in the literature
as brain cancer biomarkers and highlight reasons why the role of most markers is not yet established in the managment of CNS
tumors.
Key words: Cerebrospinal fluid; central nervous system cancers; cerebrospinal fluid cytology; biochemical markers

INTRODUCTION CSF is a readily accessible body fluid that is reflective
of the underlying pathological state of the CNS, hence it
Brain cancers are the leading cause of death by solid tumors has been widely targeted for biomarker discovery for a
in children and the cause of morbidity and mortality across variety of neurological disorders. The CSF is continuously
a wide range of adult individuals. [1,2] The identification of produced and recycled much like blood or lymph. The
[3]
biomarkers that could allow diagnosis of brain neoplasms majority of CSF is produced by the choroid plexus located
and could be informative for cancer spread or monitor on the lateral, third and fourth ventricles. The rate of CSF
therapy response is in great demand. Blood analysis for production in humans is 0.3-0.4 mL/min and the total CSF
novel biomarkers has facilitated the timely diagnosis for volume is 90-150 mL in adults and 65-150 mL in children. [4-6]
patients with several malignancies such as prostate and CSF circulates through the ventricles, the cisterns, and the
breast cancers. However, one of the challenges that subarachnoidal space at the base of the brain, then flows
[3]
contributes to the paucity of biomarkers in the serum for over the convexities of the brain and down the length of
central nervous system (CNS) malignancies is the blood- the spinal cord. [5-7] Therefore, CSF is in contact with brain
brain barrier, which is thought to prevent the release tissue and in proximity to most tumor bulks, making it
of tumor-specific molecules into the blood circulation. an ideal reservoir of tumor-related/secreted molecules.
[8]
Cerebrospinal fluid (CSF) has thus been investigated in the
search for brain tumor markers. This is an open access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as
Access this article online the author is credited and the new creations are licensed under the identical
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Website: For reprints contact: service@oaepublish.com
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How to cite this article: Shalaby T, Achini F, Grotzer MA. Targeting
cerebrospinal fluid for discovery of brain cancer biomarkers. J Cancer
DOI: Metastasis Treat 2016;2:176-87.
10.20517/2394-4722.2016.12
Received: 03-03-2016; Accepted: 02-05-2016.

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©2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc.