Molecular neurosurgery using gene therapy to treat malignant glioma

Abstract

In the last decade, the prognosis of brain tumor patients has dramatically improved due to recent advances in microsurgical techniques and the development of functioning neuroimaging, computer-assisted neuronavigation, endoscopic surgery, intravascular surgery and radiosurgery. 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 (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 2 years, despite multimodality treatment with extensive surgical resection and adjuvant therapies using radiation and immunochemotherapy. In order to overcome this formidable neoplasm, the effectiveness of molecular neurosurgery using gene therapy has been investigated since 1992. In this paper, molecular genetic studies and the current state of gene therapy for malignant brain tumors are described, and the future direction of this fascinating approach is discussed.