Abstract
Glioblastoma (GBM) is a primary neuroepithelial tumor of the central nervous system, characterized by an extremely aggressive clinical phenotype. Patients with GBM have a poor prognosis and only 3–5% of them survive for more than 5 years. The current GBM treatment standards include maximal resection followed by radiotherapy with concomitant and adjuvant therapies. Despite these aggressive therapeutic regimens, the majority of patients suffer recurrence due to molecular heterogeneity of GBM. Consequently, a number of potential diagnostic, prognostic, and predictive biomarkers have been investigated. Some of them, such as IDH mutations, 1p19q deletion, MGMT promoter methylation, and EGFRvIII amplification are frequently tested in routine clinical practice. With the development of sequencing technology, detailed characterization of GBM molecular signatures has facilitated a more personalized therapeutic approach and contributed to the development of a new generation of anti-GBM therapies such as molecular inhibitors targeting growth factor receptors, vaccines, antibody-based drug conjugates, and more recently inhibitors blocking the immune checkpoints. In this article, we review the exciting progress towards elucidating the potential of current and novel GBM biomarkers and discuss their implications for clinical practice.
Highlights
Glioblastoma (GBM) is a primary neuroepithelial tumor of the central nervous system, characterized by an extremely aggressive clinical phenotype that has arisen from interand intrapatient genomic and histopathological diversity (Figure 1; Table 1)
Diagnostic biomarkers enable more accurate tumor classification; prognostic biomarkers inform about a likely cancer outcome and predictive biomarkers facilitate patient p53 signalling altered in 87% receptor tyrosine kinase (RTK)/RAS/PI3 signalling altered in 88% RB signaling altered in 78%
There are some molecular markers still under evaluation, but several are commonly tested as part of the routine clinical interrogation of GBM patients including O6-methylguanine DNA methyltransferase (MGMT), isocitrate dehydrogenase (IDH), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), tumor suppressor protein TP53, phosphatase and tensin homolog (PTEN), p16INK4a gene, phospholipid metabolites, cancer stem cells, and recently imaging biomarkers (Table 2)
Summary
Glioblastoma (GBM) is a primary neuroepithelial tumor of the central nervous system, characterized by an extremely aggressive clinical phenotype that has arisen from interand intrapatient genomic and histopathological diversity (Figure 1; Table 1). Bevacizumab against circulating vascular endothelial growth factor (VEGF) is widely used, more recently in combination with lomustine (CCNU) [4] Despite these aggressive therapeutic regimens the majority of patients suffer recurrence due to the molecular heterogeneity of GBM tumors and penetration of therapeutic agents through the blood-brain barrier (BBB). There are some molecular markers still under evaluation, but several are commonly tested as part of the routine clinical interrogation of GBM patients including O6-methylguanine DNA methyltransferase (MGMT), isocitrate dehydrogenase (IDH), epidermal growth factor receptor (EGFR), VEGF, tumor suppressor protein TP53, phosphatase and tensin homolog (PTEN), p16INK4a gene, phospholipid metabolites, cancer stem cells, and recently imaging biomarkers (Table 2). The aim of this article is to review the exciting progress towards elucidating the potential of diagnostic, prognostic, and predictive biomarkers of GBM and discuss their implications for clinical practice
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