Abstract
Glioblastoma (GBM) is the most common and malignant type of primary brain tumor, due to its high heterogeneity and aggressive brain invasion patterns. Despite recent advances in imaging and surgical techniques, which allowed a more accurate diagnosis and enhanced tumoral resection while maintaining or even improving neurologic function, current therapeutic options for GBM lack effective long-term impact on disease control and patient survival remains around the year mark. Therefore, the development of new therapeutic strategies that provide highly specific tumor cell killing and effective/complete eradication of cancer is critical to improve the life expectancy of GBM patients. Driven by the tremendous advances in molecular biology, gene therapy has emerged as a promising strategy that uses nucleic acid delivery for the treatment of different forms of cancer, including GBM. In this regard, numerous/a wide range of therapeutic approaches involving versatile delivery vehicles, including non-replicating and oncolytic viruses, lipid- and polymer-based nanoparticles and stem cells, have been developed and tested for therapeutic potential. In this report, we review the principles behind such approaches and underscore their application to GBM treatment, by summarizing recent results obtained both in vitro and pre-clinical studies including the authors’, as well as those reported in patients. A brief discussion on the major achievements and the trends identified by these studies is intended to provide new prospects for future developments and further improvements of the existing approaches towards successful treatment of malignant brain tumors.
Highlights
Glioblastoma (GBM), the most common and malignant type of a class of tumors arising from glia or glial precursors - glioma - is one of the deadliest forms of human cancer, with a median patient survival of 12 to 15 months after diagnosis [1,2]
Pre-clinical studies in human malignant glioma xenografts involving ONYX-015, a modified oncolytic adenovirus capable of replication in p53-defective tumor cells [55] demonstrated that intratumoral viral delivery resulted in cell lysis and impaired tumor growth, the response was independent of the p53 status
Therapeutic approaches involving T cells expressing chimeric antigen receptors (CARs) for glioma-specific antigens, including IL-13Rα2, erythropoietin-producing hepatocellular carcinoma A2 (EphA2) and a truncated form of the EGFR (EGFRvIII) have shown potent antitumor activity in animal models [60,61,62], which should be confirmed in future clinical trials
Summary
Glioblastoma (GBM), the most common and malignant type of a class of tumors arising from glia or glial precursors - glioma - is one of the deadliest forms of human cancer, with a median patient survival of 12 to 15 months after diagnosis [1,2]. The generated gene therapy approaches for GBM involved delivery of different therapeutic nucleic acids, either per se or mediated by vehicles, including viruses, lipid- and polymer-based nanoparticles and stem cells.
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