Adenovirus-mediated p53 gene therapy for human gliomas

OBJECTIVE: The rationale and current evidence for using p53 gene replacemen t as a potential treatment for human gliomas are reviewed. The possible ben efits of and obstacles to this approach are delineated. METHODS: One approach to overcoming the poor outcomes associated with conve ntional glioma therapies involves the replacement of tumor suppressor genes that are fundamental to glioma development. The p53 gene is one of the mos t frequently mutated genes in human gliomas, and loss of p53 function is cr itical to the development of glial neoplasms. Consequently, replacement of the p53 gene using viral vectors may be a potential treatment for human gli omas. RESULTS: In vitro studies demonstrate that adenovirus-mediated p53 gene tra nsfer into gliomas with mutant p53 results in massive apoptosis. Similarly, transfer of p53 inhibits tumor growth in vivo. In contrast to mutant p53 g liomas, wild-type p53 glioma cells are resistant to the apoptotic effects o f p53 transfer, but this resistance can be overcome by the addition of deox yribonucleic acid-damaging agents such as ionizing radiation or chemotherap y. The main obstacle to p53 gene therapy involves the limitations associate d with current modes of delivery. CONCLUSION: Preclinical data strongly support the use of p53 gene transfer as a potential treatment for human gliomas.