Abstract
Glioblastoma multiforme is the most common and aggressive primary brain tumor. Even with aggressive treatment including surgical resection, radiation, and chemotherapy, patient outcomes remain poor, with five-year survival rates at only 10%. Barriers to treatment include inefficient drug delivery across the blood brain barrier and development of drug resistance. Because gliomas occur due to sequential acquisition of genetic alterations, gene therapy represents a promising alternative to overcome limitations of conventional therapy. Gene or nucleic acid carriers must be used to deliver these therapies successfully into tumor tissue and have been extensively studied. Viral vectors have been evaluated in clinical trials for glioblastoma gene therapy but have not achieved FDA approval due to issues with viral delivery, inefficient tumor penetration, and limited efficacy. Non-viral vectors have been explored for delivery of glioma gene therapy and have shown promise as gene vectors for glioma treatment in preclinical studies and a few non-polymeric vectors have entered clinical trials. In this review, delivery systems including viral, non-polymeric, and polymeric vectors that have been used in glioblastoma multiforme (GBM) gene therapy are discussed. Additionally, advances in glioblastoma gene therapy using viral and non-polymeric vectors in clinical trials and emerging polymeric vectors for glioma gene therapy are discussed.
Highlights
Glioblastoma multiforme (GBM) is a type of glioma that arises from astrocytes, defined by the World Health Organization (WHO) as a grade IV glioma [1,2]
Advances in gene delivery systems will be reviewed, highlighting viral and non-viral vectors used for GBM gene therapy
The current standard of care including surgical resection, adjuvant chemotherapy, and radiation does not result in remission for the majority of patients
Summary
Glioblastoma multiforme (GBM) is a type of glioma that arises from astrocytes, defined by the World Health Organization (WHO) as a grade IV glioma [1,2]. High-grade gliomas are typically located in undesirable locations in the cerebral hemisphere and are classified as diffuse gliomas due to their high rate of infiltration into surrounding brain tissue. These factors allow for persistent tumor growth and lessen the chance of remission, with progression to grade III or IV gliomas likely even in most low-grade diffuse gliomas [2,5]. Advances in gene delivery systems will be reviewed, highlighting viral and non-viral vectors used for GBM gene therapy. Trials bringing these therapies closer to clinical approval to date will be discussed, as well as preclinical studies, using polymeric nanoparticles, which have shown promise as future vectors for delivery of gene therapy in GBM patients
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