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New approaches in the treatment of glioblastoma with gene editing
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Mobina Negahbanpour   , Touraj Naderi |
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Abstract: (246 Views) |
Introduction: Glioblastoma multiforme (GBM) is one of the most invasive and devastating primary brain tumor, that there is no remedies or certain treatment for that. There are some epigenetic modifications, including DNA methylation. We have high level of methylation on some parts more than others which are called Hotpoints, like histon coils and CpG islands. Transcription of DNA is done by mRNA, new RNA, includes non-coding parts which are not expressed and they should be omitted, that it’s splicing‘s duty. If this omitting occurs wrongly, the TACC3 domain leads to FGFR3 and that part gets tumoral. FGFR3-TACC3 fusion was first described in GBM. The abnormalities of all these phenomena appears when nervous system's DNA get effected. There are some pathways that get effected by some multiple cascades ways, like Ras pathway. Ras pathway and also Cdc42 control and regulate broad cellular activities including GBM cell polarity and migration via specifying localization of filopodia. There are some other ways to become oncogenic with GBM stem cells just like UPR (unfolded protein response).
Search Method: The articles were the result of a PubMed search by using the phrases “Glioblastoma” and “Epigenic methylation” and “Gene therapy.
Results: Several strategies for treatment have been employed including suicide genes which encode enzymes for converting a prodrug into an active cytotoxic compound; immunomodulatory genes to enhance immune response for antitumor; tumor-suppressor genes; and oncolytic virotherapy using viruses which are selectively to target and to induce lysis of tumor cells.
Conclusion: Preventing the overexpression of Emx2 (empty spiracles homeobox 2) as a transcription factor, using the oncolytic PVSRIPO vector, VB-111 as an anti-angiogenic drug, using some prodrugs and drugs such as TLN-4601, doxycycline and Tetracycline is effective for treating and preventing tumor growth.
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| Keywords: GBM, DNA methylation, Cdc42, Gen fusion, Ras pathway |
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Full-Text [PDF 332 kb]
(39 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2024/01/29 | Accepted: 2023/08/1 | Published: 2023/08/1
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