Relative to their prevalence, malignant gliomas have received a disproportionate amount of attention as targets for gene therapy.<sup>9 Culver K.W. Gene therapy for malignant neoplasms of the CNS Bone Marrow Transplant 1996 ;  18 (suppl) : S6-S9

Haga clic aquí para ir a la sección de Referencias</sup> Several factors have contributed to the interest in gene therapy techniques for malignant gliomas (principally anaplastic astrocytomas and glioblastoma multiforme). Malignant gliomas are good candidates for gene therapy because their growth is relatively well localized. Although they infiltrate the surrounding brain, thereby making complete surgical excision impossible, they rarely metastasize outside the brain. This tremendously simplifies the targeting of gene vectors to the tumor. Systemic delivery of genetic vectors to widespread metastases is currently not achievable with high efficiency and low toxicity (see article by Drs. Wivel and Wilson on p 483 of this issue). The local delivery to the bulk of the tumor, however, can be achieved through either stereotactic injection of vectors into the brain tumor or infiltration of the tumor with genetic vector at the time of gross total resection. This approach bypasses the blood–brain barrier that limits the entry of many otherwise potentially useful chemotherapy agents. In addition, direct injection of genetic vectors limits systemic exposure to the therapeutic agent and, therefore, minimizes systemic toxicity. Malignant gliomas have extremely high mortality rates that have not been affected significantly by newer surgical, radiation, or drug therapies; thus, experimental, high-risk therapies are more reasonable options for patients with malignant glioma. Currently, several of the glioma gene therapy clinical trials treat patients as part of their initial therapy.

Brain tumors comprise a broad spectrum of biologic and clinical features making it unlikely for a single therapeutic approach to be applicable to all patients. Several molecular approaches to these tumors are being developed, including enzyme-prodrug therapy, targeting tumor suppressor and angiogenesis functions, immunotherapy, and the use of oncolytic viruses. This article discusses the preclinical work to develop these approaches and the early clinical trials.