Abstract
Introduction: High-grade gliomas (HGGs) still have a high rate of recurrence and lethality. Gene therapies were projected to overcome the therapeutic resilience of HGGs, due to the intrinsic genetic heterogenicity and immune evasion pathways. The present literature review strives to provide an updated overview of the novel gene therapies for HGGs treatment, highlighting evidence from clinical trials, molecular mechanisms, and future perspectives. Methods: An extensive literature review was conducted through PubMed/Medline and ClinicalTrials.gov databases, using the keywords “high-grade glioma,” “glioblastoma,” and “malignant brain tumor”, combined with “gene therapy,” “oncolytic viruses,” “suicide gene therapies,” “tumor suppressor genes,” “immunomodulatory genes,” and “gene target therapies”. Only articles in English and published in the last 15 years were chosen, further screened based on best relevance. Data were analyzed and described according to the PRISMA guidelines. Results: Viruses were the most vehicles employed for their feasibility and transduction efficiency. Apart from liposomes, other viral vehicles remain largely still experimental. Oncolytic viruses and suicide gene therapies proved great results in phase I, II preclinical, and clinical trials. Tumor suppressor, immunomodulatory, and target genes were widely tested, showing encouraging results especially for recurrent HGGs. Conclusions: Oncolytic virotherapy and suicide genes strategies are valuable second-line treatment options for relapsing HGGs. Immunomodulatory approaches, tumor suppressor, and target genes therapies may implement and upgrade standard chemoradiotherapy. Future research aims to improve safety profile and prolonging therapeutic effectiveness. Further clinical trials are needed to assess the efficacy of gene-based therapies.
Highlights
High-grade gliomas (HGGs) still have a high rate of recurrence and lethality
High-grade gliomas (HGGs) are deadly brain tumors accounting for 70% of all central nervous system neoplasms [1,2,3], and the optimization of their management is among the most demanding challenging of the modern neuro-oncology
Gene therapies are projected with the aim to edit the glioma genome and overcome the therapeutic resilience of HGGs
Summary
High-grade gliomas (HGGs) still have a high rate of recurrence and lethality. Gene therapies were projected to overcome the therapeutic resilience of HGGs, due to the intrinsic genetic heterogenicity and immune evasion pathways. High-grade gliomas (HGGs) are deadly brain tumors accounting for 70% of all central nervous system neoplasms [1,2,3], and the optimization of their management is among the most demanding challenging of the modern neuro-oncology. The reasons for their resilience toward treatment strategies depend on the high cell turnover, pathological neoangiogenesis, and genetic landscape heterogenicity [4,5,6,7,8,9,10,11]. Nanotechnologies, biotechnologies, and translational medicine provided the means for the development of more sophisticated approaches, including gene therapies which have polarized growing attention during the last few years [18,19,20,21,22,23,24,25,26].
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