Nanoparticle delivery of suicide DNA for epithelial ovarian cancer therapy

Abstract

The standard treatment for patients with advanced stage epithelial ovarian cancer is optimal surgical debulking followed by chemotherapy with paclitaxel plus a platinum-based therapy (cisplatin or carboplatin). Although ∼80% of patients receiving this therapeutic regimen have an initial favorable response, recurrent disease will occur in a majority of cases. Regrettably, there are currently no effective therapies for those patients with advanced-stage ovarian cancer, who either do not respond to initial therapy or for those who develop recurrent disease. There is an immediate need for a more effective treatment for this deadly disease. Gene therapy holds great promise as an alternative treatment for metastatic ovarian cancer. Metastatic tumors in this disease are nearly always confined to the peritoneal cavity, so intraperitoneal delivery of therapeutic DNA allows for direct treatment of the tumors. In addition, this delivery route protects healthy organs outside the cavity from harmful side effects. In theory, the ability to target the delivery of DNA to tumor cells, as well as the ability to control its expression once inside the cell, provides an added level of therapeutic efficiency and specificity that is difficult to achieve using chemotherapy. In practice, however, the full potential of these advantages of DNA therapies has yet to be achieved and remains a goal of preclinical and clinical studies. An important consideration in any gene therapy protocol is the choice of vector used to deliver the DNA to cells. With a few exceptions, viral vectors (either adenoviral or retroviral) have been used in clinical trials for the treatment of ovarian cancer (see http://clinicaltrials. gov). Recently, the use of nonviral vectors for the delivery of therapeutic genes is receiving wide attention by the research community, particularly in light of the serious consequences that have occurred in association with the use of viral vectors in patients. © 2008 Springer Science + Business Media, LLC.