Gene Therapy for Skull Base Tumors

Abstract

During the last 10 years, gene therapy has certainly risen to the forefront of basic science and clinical medicine. Designing more efficient gene delivery systems is currently the "holy grail" of genetic therapeutics, because even the most efficient viral vectors do not transfect all cells at the treatment site, which leads to local recurrence in the case of most brain tumors. The use of oncolytic viruses that propagate through tumors may have the best potential for treating skull base lesions in the future. Because many skull base tumors are histologically benign, gene therapy approaches for these tumors may be an excellent first step, as partial killing leading to local control with minimal morbidity and mortality may soon be possible. The accessibility of these tumors by endovascular approaches is also currently feasible, which could lead to high vector concentrations within the tumor bed, although limiting vector administration and gene expression in the adjacent brain. With advances in vector development, limiting gene expression to tumor cells with transcriptional or transductional targeting, and the application of more toxic gene therapy paradigms, the treatment of many skull base tumors may soon be possible.