Abstract
Glioblastoma multiforme (GBM) is the most common high-grade intracranial tumor in adults. It is characterized by uncontrolled proliferation, diffuse infiltration due to high invasive and migratory capacities, as well as intense resistance to chemo- and radiotherapy. With a five-year survival of less than 3% and an average survival rate of 12 months after diagnosis, GBM has become a focus of current research to urgently develop new therapeutic approaches in order to prolong survival of GBM patients. The methylation status of the promoter region of the O6-methylguanine–DNA methyltransferase (MGMT) is nowadays routinely analyzed since a methylated promoter region is beneficial for an effective response to temozolomide-based chemotherapy. Furthermore, several miRNAs were identified regulating MGMT expression, apart from promoter methylation, by degrading MGMT mRNA before protein translation. These miRNAs could be a promising innovative treatment approach to enhance Temozolomide (TMZ) sensitivity in MGMT unmethylated patients and to increase progression-free survival as well as long-term survival. In this review, the relevant miRNAs are systematically reviewed.
Highlights
Cancer is one of the leading causes of death worldwide with 14 million new cases diagnosed and eight million deaths every year
The relevant literature investigating the relationship between different miRNAs and glioblastoma was systematically reviewed and the results were analyzed to evaluate the value of different miRNAs in the treatment of Glioblastoma multiforme (GBM)
That GBM secrete exosomes, microvesicles, apoptotic bodies and oncosomes containing the glioma-specific receptor of epidermal growth factor (EGFRvIII), miR-21 as well as mutant IDH1 mRNA [53]
Summary
Cancer is one of the leading causes of death worldwide with 14 million new cases diagnosed and eight million deaths every year. An unmethylated MGMT promoter is an inherent prognostic indicator for poor overall-survival, which demonstrates the urgent need for the identification of new prognostic factors, especially for these patients. For this specific patient group, tailored study concepts have been performed with intensified TMZ or with concepts omitting TMZ but adding novel potentially effective substances such as Vascular Endothelial Growth Factor (VEGF)-inhibitors, integrin-antagonists or other molecular targeted substances. The up- or down-regulation of miRNAs in tumor cells is deterministic for either a tumor-suppressive or an oncogenic characteristic of the respective miRNA [12] In this manuscript, the relevant literature investigating the relationship between different miRNAs and glioblastoma was systematically reviewed and the results were analyzed to evaluate the value of different miRNAs in the treatment of GBM
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