Targeting cerebrospinal fluid for discovery of brain cancer biomarkers

Abstract

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. 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.

Circulating tumour DNA, microRNA and metabolites in cerebrospinal fluid as biomarkers for central nervous system malignancies

“…Conclusive results cannot clearly be gathered for further clinical validation. A multi-institutional, longitudinal, collaborative study of a large cohort of patients is needed 9. Moreover, more comprehensive studies are required to specifically examine the impact of tumour type and tumour location in CNS in order to establish the reliability of different markers for each individual type of CNS tumour.…”

Peripheral biomarkers for pediatric brain tumors: current advancements and future challenges

“…Immunohistochemical assays are also possible, making the cytologic analysis of CSF somewhat comparable to tissue biopsy in the range of qualitative information it can provide. However, CSF cytology has a low sensitivity (45%), unless performed repeatedly on the same patient, making it an inaccurate and impractical brain tumor screening modality by itself [16,17] .…”

MicroRNAs in Cerebrospinal Fluid as Biomarkers in Brain Tumor Patients

“…Hlavní funkce CSF je zejména mechanická, chrání mozek před nárazy, dále přispívá k udržování stálého nitrolebního tlaku a slouží jako prostředek k transportu bio molekul a odvádění metabolitů. Vzhledem k tomu, že CSF omývá celou centrální nervovou soustavu (CNS), a dostává se tedy do blízkého kontaktu s jakoukoli možnou patologickou tkání, je považován za ideální zdroj bio logického materiálu pro následné dia gnostické účely [5][6][7].…”

“…jeho senzitivita pro dia gnostiku glioblastomu (GBM) se pohybuje pouze okolo 10 % [11]. Další nevýhodou je, že rychlost a uvolňování maligních buněk do CSF je intermitentní proces, což může vést k vysoké míře chybovosti této metody [5,6,11].…”

“…Například hladina miR-21 u pacientů s gliomy dokázala rozlišit nádorové vzorky CSF s vyšší citlivostí a specificitou než hladiny miR-21 detekované v krevní plazmě [21]. Analýza c-miRNA v CSF proto představuje slibný nástroj potenciálně vedoucí ke zdokonalení současné dia gnostiky nádorů mozku [5,6].…”