Current Status of Gene Therapy for Brain Tumors

Brain tumors, solid neoplasms within the brain or the central spinal canal, can often be debilitating and difficult to treat. Glioblastoma (GBM) is the most aggressive and deadliest primary brain tumor in adults, not responding to current therapies and with a very low percentage of 5-year survivors. Therefore, the development of new treatments is critical. Gene therapy is a treatment strategy that relies on the delivery of genetic material into cells for therapeutic purposes, and has demonstrated increasing success in preclinical models and clinical trials. Within this strategy, we include selectively replication-competent oncolytic viruses. While the oncolytic viruses act directly as antitumor agents due to virus replication, the effects are due to the transfer of viral genetic material to the cells. GBM is a good target for gene therapy because tumors remain locally within the brain and only rarely metastasize to other tissues; the majority of cells in the brain are postmitotic, which allows for specific targeting of dividing tumor cells; and tumors can often be accessed neurosurgically for administration of therapy. This chapter will focus on GBM and describe current gene therapy strategies used for brain tumors, including cytotoxic, immune-stimulatory, tumor microenvironment disrupting gene therapy, oncolytic viruses, small RNA interference, and delivery systems encompassing viruses, stem cells, and nanotechnology, as well as current challenges and future directions.