Insights into molecular therapy of glioma: current challenges and next generation blueprint

Abstract

Glioma accounts for the majority of human brain tumors. With prevailing treatment regimens, the patients have poor survival rates. In spite of current development in mainstream glioma therapy, a cure for glioma appears to be out of reach. The infiltrative nature of glioma and acquired resistance substancially restrict the therapeutic options. Better elucidation of the complicated pathobiology of glioma and proteogenomic characterization might eventually open novel avenues for the design of more sophisticated and effective combination regimens. This could be accomplished by individually tailoring progressive neuroimaging techniques, terminating DNA synthesis with prodrug-activating genes, silencing gliomagenesis genes (gene therapy), targeting miRNA oncogenic activity (miRNAmRNA interaction), combining Hedgehog-Gli/Akt inhibitors with stem cell therapy, employing tumor lysates as antigen sources for efficient depletion of tumor-specific cancer stem cells by cytotoxic T lymphocytes (dendritic cell vaccination), adoptive transfer of chimeric antigen receptor-modified T cells, and combining immune checkpoint inhibitors with conventional therapeutic modalities. Thus, the present review captures the latest trends associated with the molecular mechanisms involved in glial tumorigenesis as well as the limitations of surgery, radiation and chemotherapy. In this article we also critically discuss the next generation molecular therapeutic strategies and their mechanisms for the successful treatment of glioma.

MiRNAs Mediate GDNF-Induced Proliferation and Migration of Glioma Cells

“…The results revealed that participate in colorectal cancer, prostate cancer, pancreatic cancer, glioma, and other cancer-related pathways. Among these, MAPK, Wnt, and mammalian target of rapamycin (mTOR) signaling pathways are closely related to glioma occurrence and development [49]. These signaling cascades primarily down-regulate tumor-suppressor genes and up-regulate tumor-causing genes in glioma [11, 15, 50-52].…”

Cerium Oxide Nanoparticles as Novel Tool in Glioma Treatment: An In vitro Study

“…However and in many cases; chemotherapy of those tumors is problematic; as the anticancer drugs are often hydrophobic molecules leading to restricted access to brain tissues [55]. Even though accompanied by severe side effects; a combination of surgery; radiotherapy and the use of chemotherapeutical drugs [31,32,56] remain the main options in treatment of those tumors [57]. In that context; the alkylating prodrug temozolomide crosses the blood-brain barrier (BBB) and disintegrates spontanously (non-enzymatic) in methyl hydrazine which alkylates DNA bases finally resulting in inhibition of DNA replication and in triggering of cell death.…”

New analysis framework incorporating mixed mutual information and scalable Bayesian networks for multimodal high dimensional genomic and epigenomic cancer data

“…For the purposes of this particular analysis, we decided to concentrate on three types of molecular data, one discrete (somatic mutations) and two -continuous (RNA-seq gene expression, and promoter methylation). This selection is reflective of the recent trends in multimodal cancer data analyses [21,26], makes sense in the broad cancer genetics context [27][28][29][30][31][32], and underscores the comparative importance of the methylation molecular data [29].…”