[Oncolytic adenovirus for the treatment of cerebral tumors: past, present and future]

Abstract

The transfer of genetic material as a therapy (gene therapy) is one of the experimental treatments being considered in patients with brain tumors resistant to any conventional treatment. Several clinical trials have proved that the intratumoral administration of genes is fairly safe for patients, however the anti-tumor effect of these strategies remains suboptimal. One of the main problems in cancer gene therapy is the failure of current vectors to achieve enough tumor transduction in a suficient number of cells. This is even true for vectors derived from viruses with high infectivity ability such as adenovirus. For that reason, current strategies explore the use of adenoviruses able to replicate and spread throughout the tumor. The local, intratumoral injection of adenovirus is an especially suitable strategy for gliomas because these tumors, although infiltrative, rarely metastasize. Two approaches have been used to generate tumor-selective replicative adenoviruses: use of tumor-specific promoters to regulate the expression of viral genes, and the deletion of the viral functions required for the activation of the cell cycle. Since normal cells surrounding giomas are quiescent, the second strategy is particularly attractive to develop new treatments for brain tumors.