Gene Therapy for Glioblastoma
Established treatments such as surgery, radiation, and chemotherapy have only minimally altered the median survival time of patients with glioblastoma multiforme, the most common malignant brain tumor. These failures reflect the highly invasive nature of the disease, as well as the fact that few cells are actively dividing at any given time. As a result, therapies need to act in areas of the brain that are spatially separated from the site of tumor origin and over extended periods of time temporally separated from their introduction. Over the past decade, laboratory studies and early clinical trials have raised the hope that these therapeutic requirements may be fulfilled by gene therapy in which nonreplicating transgene-bearing viruses, oncolytic viruses, or migratory stem cells are used to deliver tumoricidal transgenes. The authors review the principles behind these approaches and their initial results.
Disappointing results in the treatment of glioblastoma multiforme with surgery, radiation, and chemotherapy have fueled a search for new treatment modalities. One intriguing modality for treating glioblastoma is gene therapy. In gene therapy for cancer, viral vectors are administered systemically or intratumorally by surgeons. These viral vectors can be nonreplicating viruses that deliver transgenes whose expression leads to an anticancer effect, or they can be replicating oncolytic viruses that achieve an anticancer effect through viral replication leading to cellular lysis. Glioblastoma multiforme represents an excellent target for cancer gene therapy in which viral vectors are used that only propagate in dividing cells, because glioblastoma cells are among the few rapidly proliferating ones in the CNS, where only some microglia and endothelial cells have the ability to divide. In this review we focus on laboratory advances and clinical trials in which nonreplicating and oncolytic viral vectors are used in the treatment of glioblastoma (the most common malignant brain tumor) as well as cellular delivery vehicles that can be used to target these lesions.
Established treatments such as surgery, radiation, and chemotherapy have only minimally altered the median survival time of patients with glioblastoma multiforme, the most common malignant brain tumor. These failures reflect the highly invasive nature of the disease, as well as the fact that few cells are actively dividing at any given time. As a result, therapies need to act in areas of the brain that are spatially separated from the site of tumor origin and over extended periods of time temporally separated from their introduction. Over the past decade, laboratory studies and early clinical trials have raised the hope that these therapeutic requirements may be fulfilled by gene therapy in which nonreplicating transgene-bearing viruses, oncolytic viruses, or migratory stem cells are used to deliver tumoricidal transgenes. The authors review the principles behind these approaches and their initial results.
Disappointing results in the treatment of glioblastoma multiforme with surgery, radiation, and chemotherapy have fueled a search for new treatment modalities. One intriguing modality for treating glioblastoma is gene therapy. In gene therapy for cancer, viral vectors are administered systemically or intratumorally by surgeons. These viral vectors can be nonreplicating viruses that deliver transgenes whose expression leads to an anticancer effect, or they can be replicating oncolytic viruses that achieve an anticancer effect through viral replication leading to cellular lysis. Glioblastoma multiforme represents an excellent target for cancer gene therapy in which viral vectors are used that only propagate in dividing cells, because glioblastoma cells are among the few rapidly proliferating ones in the CNS, where only some microglia and endothelial cells have the ability to divide. In this review we focus on laboratory advances and clinical trials in which nonreplicating and oncolytic viral vectors are used in the treatment of glioblastoma (the most common malignant brain tumor) as well as cellular delivery vehicles that can be used to target these lesions.