Abstract
Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to effective surgical resection. The present review summarizes recent advances in our understanding of the molecular mechanisms of therapeutic resistance of GBM to already known drugs, the molecular characteristics of glioblastoma cells, and the barriers in the brain that underlie drug resistance. We also discuss the progress that has been made in the development of new targeted drugs for glioblastoma, as well as advances in drug delivery across the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB).
Highlights
Glioblastoma multiforme (GBM) is the most common and devastating primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and does not lend itself to effective surgical resection
The latter is more commonly activated after treatment and is associated with acquired resistance driven by mismatch repair (MMR) defects in chemotherapy-sensitive gliomas that recur after treatment with temozolomide
The interaction of FAM289 with galectin-1 facilitates its entry into the nucleus where FAM289 activates the extracellular signal-regulated kinase (ERK) pathway, upregulates DNA methyl transferase 1 (DNMT1) expression, and induces the formation of the cancer stem cells (CSCs) phenotype, which leads to drug resistance of glioma cells to TMZ [99]
Summary
Glioblastoma multiforme (GBM) is the most common and devastating primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and does not lend itself to effective surgical resection. According to the data of the National Cancer Institute, about 23,890 adults were diagnosed with new cases of brain and other nervous system cancer in 2020. The incidence of GBM ranges from two to three per 100,000 adults per year, and this tumor for 52% of all primary brain tumors. About 17% of all tumors of the brain (primary and secondary) are GBM and develop mostly in people from 45 and 70 years of age. It is necessary to carry out a differential diagnosis of GBM from intracranial mass lesions; here, collection and analysis of tumor tissue via brain biopsy or surgical resection can come to the rescue. GBM is one of the best characterized genomic cancers, several types are distinguished according to their transcriptional profile (proneural, neural, classical, and mesenchymal or edge, edge-like, core, core-like), genetics (mutations in IDH gene), and epigenetics (CpG island methylation phenotype (CIMP), O6 methylguanine-DNA methyltransferase (MGMT) promoter methylation) [8,9,10,11,12]
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