**Author details**

addition, quantification of as few as seven microRNAs in CSF (miR-10b, miR-21, miR-125b, miR-141, miR-200a, miR-200b, and miR-200c) enabled differential recognition of GBM and

Akers et al. analyzed extracellular vesicles (EVs) containing miRNAs in the CSF from patients with GBMs. The EV fraction was isolated by differential centrifugation. Although the analytic algorithm for quantitatively assessing EV miRNA remains underdeveloped, the authors showed that the CSF miR-21 levels of patients with GBM were 10-fold higher than those in the

Recently, another study reported results to those of Akers and coworkers. Exosomal miR-21 levels in the CSF of patients with glioma were found to be significantly higher than in controls, although no difference was detected in serum-derived exosomal miR-21 expression. Interest‐ ingly, the CSF-derived exosomal miR-21 levels correlated with a level of dissemination and a location of recurrence. Therefore, exosomal miR-21 in CSF may be a predictive marker for the

Over the past decade, our understanding of genetic alterations and the tumor-specific signal pathways in glioma has been made, although this knowledge to date has not been translated into the prognosis of the patients with glioma. However, a better understanding of key pathways associated with gliomagenesis and malignant transformation could promise further improvements in glioma therapy. Maximum safe resection followed by radiotherapy up to a total dose of 60 Gy and TMZ-based chemotherapy have been established as a standard therapy, but new molecular targeting drugs, including small-molecule cell cycle inhibitors and biological and immune-based therapies have begun to yield promising results in clinical

Over the past two decades, miRNAs have emerged as molecules central to glioma biology. miRNAs represent an additional layer of complexity in tumor biology and have been further validated as regulators of processes fundamental to glioma. This field is rapidly changing. Herein, we have reviewed the emerging roles of miRNAs as drivers of glioma formation and progression with a focus on glioma hallmarks. miRNAs may be essential in glioma growth, angiogenesis, invasion, genomic instability, tumor-promoting inflammation, and gliomaspecific metabolism. In recent years, functions of miRNAs in gliomagenesis and microenvir‐ onment have been considerably elucidated, and we have validated the tumor suppressive or oncogenic functions of miRNAs in glioma. Now, we should move toward a next phase involving clinical trials with miRNAs as glioma therapies. For example, miR-34, a tumorsuppressive miRNA that simultaneously downregulates the expressions of MET, PDGFRA, and CDK6 is currently in clinical trials as a directed therapy for advanced solid tumors. In glioma, the restoration of miR-34a can possibly outperform any single targeted agents tailored to those targets. There remain several problems to use miRNAs in glioma therapy. These include not only accumulation of our knowledge of miRNAs' biological functions in glioma,

metastatic brain tumor with high accuracy (91%–99%) (171).

early stages of tumor recurrence or metastasis (173).

CSF of nononcologic patients (172).

52 Neurooncology - Newer Developments

**5. Future prospects**

studies.

Takashi Sasayama\* , Kazuhiro Tanaka and Eiji Kohmura

\*Address all correspondence to: takasasa@med.kobepu.ac.jp

Department of Neurosurgery, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo-ku, Kobe, Japan
