Adenovirus-mediated p53 gene therapy for human gliomas

Abstract

Objective: The rationale and current evidence for using p53 gene replacement as a potential treatment for human gliomas are reviewed. The possible benefits of and obstacles to this approach are delineated.

Methods: One approach to overcoming the poor outcomes associated with conventional glioma therapies involves the replacement of tumor suppressor genes that are fundamental to glioma development. The p53 gene is one of the most frequently mutated genes in human gliomas, and loss of p53 function is critical to the development of glial neoplasms. Consequently, replacement of the p53 gene using viral vectors may be a potential treatment for human gliomas.

Results: In vitro studies demonstrate that adenovirus-mediated p53 gene transfer into gliomas with mutant p53 results in massive apoptosis. Similarly, transfer of p53 inhibits tumor growth in vivo. In contrast to mutant p53 gliomas, wild-type p53 glioma cells are resistant to the apoptotic effects of p53 transfer, but this resistance can be overcome by the addition of deoxyribonucleic acid-damaging agents such as ionizing radiation or chemotherapy. The main obstacle to p53 gene therapy involves the limitations associated with current modes of delivery.

Conclusion: Preclinical data strongly support the use of p53 gene transfer as a potential treatment for human gliomas.