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Strategies in gene therapy for glioblastoma
Aneta Kwiatkowska1, Mohan S Nandhu, Prajna Behera
1Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. mviapiano@partners.org.
Abstract:
Glioblastoma (GBM) is the most aggressive form of brain cancer, with a dismal prognosis and extremely low percentage of survivors. Novel therapies are in dire need to improve the clinical management of these tumors and extend patient survival. Genetic therapies for GBM have been postulated and attempted for the past twenty years, with variable degrees of success in pre-clinical models and clinical trials. Here we review the most common approaches to treat GBM by gene therapy, including strategies to deliver tumor-suppressor genes, suicide genes, immunomodulatory cytokines to improve immune response, and conditionally-replicating oncolytic viruses. The review focuses on the strategies used for gene delivery, including the most common and widely used vehicles (i.e., replicating and non-replicating viruses) as well as novel therapeutic approaches such as stem cell-mediated therapy and nanotechnologies used for gene delivery. We present an overview of these strategies, their targets, different advantages, and challenges for success. Finally, we discuss the potential of gene therapy-based strategies to effectively attack such a complex genetic target as GBM, alone or in combination with conventional therapy.
Insights
Gene therapy offers new hope for glioblastoma (GBM), the deadliest brain cancer. This review explores gene delivery strategies like oncolytic viruses and nanotechnologies to improve patient survival.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Glioblastoma (GBM) is an aggressive brain cancer with poor prognosis.
- Current treatments have limited efficacy, necessitating novel therapeutic strategies.
- Gene therapy presents a promising avenue for improving GBM treatment outcomes.
Purpose of the Study:
- To review current gene therapy approaches for glioblastoma.
- To discuss various gene delivery strategies and their associated challenges.
- To evaluate the potential of gene therapy in managing GBM, alone or in combination with conventional treatments.
Main Methods:
- Review of existing literature on gene therapy for glioblastoma.
- Analysis of gene delivery vehicles, including viral vectors, stem cells, and nanotechnologies.
- Examination of therapeutic gene strategies: tumor suppressors, suicide genes, and immunomodulatory cytokines.
Main Results:
- Gene therapy strategies for GBM include delivering tumor-suppressor genes, suicide genes, and cytokines.
- Common gene delivery vehicles are replicating and non-replicating viruses, with emerging use of stem cells and nanotechnologies.
- Variable success has been observed in pre-clinical models and clinical trials.
Conclusions:
- Gene therapy holds significant potential for treating glioblastoma.
- Optimizing gene delivery and therapeutic strategies is crucial for clinical success.
- Combination therapy integrating gene therapy with conventional treatments may enhance efficacy.
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