Abstract

Glioblastoma is a primary Central Nervous System (CNS) malignancy with poor survival. Treatment options are scarce and despite the extremely heterogeneous nature of the disease, clinicians lack prognostic and predictive markers to characterize patients with different outcomes. Certain immunohistochemistry, FISH, or PCR-based molecular markers, including isocitrate dehydrogenase1/2 (IDH1/2) mutations, epidermal growth factor receptor variant III (EGFRvIII) mutation, vascular endothelial growth factor overexpression (VEGF) overexpression, or (O6-Methylguanine-DNA methyltransferase promoter) MGMT promoter methylation status, are well-described; however, their clinical usefulness and accuracy is limited, and tumor tissue samples are always necessary. Liquid biopsy is a developing field of diagnostics and patient follow up in multiple types of cancer. Fragments of circulating nucleic acids are collected in various forms from different bodily fluids, including serum, urine, or cerebrospinal fluid in order to measure the quality and quantity of these markers. Multiple types of nucleic acids can be analyzed using liquid biopsy. Circulating cell-free DNA, mitochondrial DNA, or the more stable long and small non-coding RNAs, circular RNAs, or microRNAs can be identified and measured by novel PCR and next-generation sequencing-based methods. These markers can be used to detect the previously described alterations in a minimally invasive method. These markers can be used to differentiate patients with poor or better prognosis, or to identify patients who do not respond to therapy. Liquid biopsy can be used to detect recurrent disease, often earlier than using imaging modalities. Liquid biopsy is a rapidly developing field, and similarly to other types of cancer, measuring circulating tumor-derived nucleic acids from biological fluid samples could be the future of differential diagnostics, patient stratification, and follow up in the future in glioblastoma as well.

Highlights

  • Glioblastoma (GBM) is a devastating primary central nervous system malignancy

  • Despite the recent advances in the understanding of the disease—such as the development of molecular subgroups, characterization of common mutations, mapping of signaling pathways that lead to increased invasiveness, identifying molecules that contribute to glioma invasion—clinicians have yet failed to see any improvement in treatment options and patient outcomes [7,8]

  • Several reasons for the low rates of detectable metastasis, for example, might be the low survival rates of GBM patients, due to the presence of the blood–brain barrier (BBB), which makes it more difficult for the cells to intravasate into the circulation, or it is possible that GBM cells require critical neural-specific growth factors that are absent outside the brain

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Summary

Glioblastoma—Background

Glioblastoma (GBM) is a devastating primary central nervous system malignancy. Fighting the disease is challenging both for patients and the health care system. GBM belongs to the diffusely growing gliomas of the Central Nervous System (CNS), a heterogeneous group of tumors that are of glial, most commonly astrocytic or oligodendroglial origin [4,5]. This spectrum of diseases is characterized by their growth pattern, namely that the tumor cells aggressively invade the neighboring brain parenchyma, resulting in an extensive peritumoral infiltration. Despite the recent advances in the understanding of the disease—such as the development of molecular subgroups, characterization of common mutations, mapping of signaling pathways that lead to increased invasiveness, identifying molecules that contribute to glioma invasion—clinicians have yet failed to see any improvement in treatment options and patient outcomes [7,8]. Only some clinical factors have been identified with some correlation to patient outcomes, and the number of molecular markers that can be used as prognostic or predictive marker in glioblastoma is very limited

Molecular Markers in Glioblastoma
Circulating RNA
Extracellular Vesicles
Circulating Tumor Cells
Findings
Summary
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