Human Gene Therapy for Malignant Gliomas

Abstract

In the recent years, the prognosis of brain tumor patients has dramatically improved due to recent advances in neurosurgical operative procedures, which are included microneurosurgical techniques, development of intraoperative computer-assisted neuronavigation system (like as Neuronavigator), functional mapping, and neuro monitoring system during operative procedure. Furthermore, development of neuroendoscopic surgery, intravascular surgery and radiosurgery are also assisted the improvement of survival and/or functional prognostic rate of brain tumor patients. According to a report by the Committee of Brain Tumor Registry of Japan, the ten year survival rate of patients with benign brain tumors (meningioma, neurinoma and pituitary adenoma) is more than 95%. In contrast, patients with glioma (which constitute 33% of primary brain tumor cases) still have a poor prognosis, especially in the case of malignant, which is included anaplastic astrocytoma and glioblastoma. This poor prognosis is related to the fact that malignant glioma cells aggressively infiltrate into normal brain tissues, making total removal of the tumor impossible. The median survival time of glioblastoma patients is less than two years, despite multimodality treatment with extensive surgical resection and adjuvant therapies using radiotherapy, chemotherapy, immunotherapy, hyperthermia and so on. In order to overcome this formidable neoplasm, the effectiveness of molecular biology using gene therapy has been investigated since 1992 in U.S.A. and 2000 in Japan. In this paper, molecular genetic studies and current state of gene therapy for brain tumors is described.