Abstract
Simple SummaryGlioblastoma is the most malignant cancer of the brain and current therapeutic strategies are clearly inadequate. In addition to surgical intervention, conventional drugs and ratio-therapy, scientists are looking at approaches based on gene therapy with genetically modified viruses. In this review we give a snapshot of the current state of play in this field of research and the available information about the clinical trials. We make some suggestions as to what opportunities could be explored further and hope that this review will stimulate discussion and conception of new life saving strategies.In this review, we scrutinize the idea of using viral vectors either as cytotoxic agents or gene delivery tools for treatment of glioblastoma multiforme (GBM) in light of the experience that our laboratory has accumulated over ~20 years when using similar vectors in experimental neuroscience. We review molecular strategies and current clinical trials and argue that approaches which are based on targeting a specific biochemical pathway or a characteristic mutation are inherently prone to failure because of the high genomic instability and clonal selection characteristics of GBM. For the same reasons, attempts to develop a viral system which selectively transduces only GBM cells are also unlikely to be universally successful. One of the common gene therapy approaches is to use cytotoxic viruses which replicate and cause preferential lysis of the GBM cells. This strategy, in addition to its reliance on the specific biochemical makeup of the GBM cells, bears a risk of necrotic cell death accompanied by release of large quantities of pro-inflammatory molecules. On the other hand, engaging the immune system in the anti-GBM response seems to be a potential avenue to explore further. We suggest that a plausible strategy is to focus on viral vectors which efficiently transduce brain cells via a non-selective, ubiquitous mechanism and which target (ideally irreversibly) processes that are critical only for dividing tumor cells and are dispensable for quiescent brain cells.
Highlights
Glioblastoma multiforme (GBM) is a highly malignant primary brain cancer of predominantly astrocytic origin [1]
Attempts to develop gene therapy with the aid of viral vectors have been under development for some time, and below, we summarize some of the main strategies and their outcomes
G207 is an oncolytic recombinant replication-competent Herpes simplex simplex virus virus 11 (HSV-1) which has two modifications to increase specificity towards GBM cells: deletions in both copies of the RL1 gene to target protein kinase R (PKR)-defective cancer cells and disruption of UL39 gene to eliminate the possibility to replicate in non-dividing normal cells
Summary
Glioblastoma multiforme (GBM) is a highly malignant primary brain cancer of predominantly astrocytic origin [1]. As of today, most of the treatment algorithms are not based on molecular histological characteristics and are essentially universal, consisting of maximal surgical resection, followed by radiotherapy and chemotherapy with TMZ, followed by TMZ, known as the “Stupp protocol” [5,6]. Even though classic metastases are exceedingly rare in GBM, its cells have a tendency to migrate into the parenchyma and eventually spread extensively throughout the brain For this reason, already upon primary diagnosis, some patients have infiltration in more than one part of the brain, with tumor cells moving across the corpus callosum or through the walls of the ventricles. Is the scope for locally delivered therapies, such as slow-release formulations of anti-cancer drugs [10], photodynamic therapy [11] or viral vectors, which are the topic of this review
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
