Anti-angiogenic gene therapy in the treatment of malignant gliomas.

More than four decades ago, Dr. Judah Folkman hypothesized that angiogenesis was a critical process in tumor growth. Since that time, there have been significant advances in understanding tumor biology and groundbreaking research in cancer therapy that have validated his hypothesis. However, in spite of extensive research, glioblastoma multiforme (GBM), the most common and malignant primary brain tumor, has gained little in the way of improved median survival. There have been several angiogenesis targets that have resulted in drugs that are in clinical trials or FDA approved for clinical use in several cancers. GBM is a highly angiogenic tumor and several drugs are showing promise in clinical trials with one (bevacizumab), clinically approved for use. We will review several possible angiogenic targets in GBM as well as the vector methodologies used for delivery. In addition, GBMs present several therapeutic challenges related to structure, tumor immune microenvironment and resistance to angiogenesis. To overcome these challenges will require novel approaches to improve therapeutic gene expression and vector biodistribution in the glioma.