Novel gene-directed enzyme prodrug therapies against prostate cancer

Abstract

There is no effective cure for late-stage hormone (androgen) refractory prostate cancer. Although chemotherapy offers palliation to these late-stage patients, it also leads to systemic toxicities leading to poor quality of life. Clearly, the focus is on the development and evaluation of novel biologically relevant alternatives such as cytoreductive gene-directed enzyme prodrug therapy (GDEPT). With the current limitations of effective gene delivery in vivo, the in situ amplification of cytotoxicity due to bystander effects of GDEPT has special attraction for patients with prostate cancer, the prostate being dispensable. This review focuses on the development, application and potential of various GDEPTs for treating prostate cancer. The current status of research related to the issues of enhancement of in situ GDEPT delivery and prostate cancer-specific targeting of vectors (especially viral vectors) is assessed. Finally, the scope and progress of synergies between GDEPT and other treatment modalities, both traditional and alternate, are discussed.

Keywords::

• 5-fluorocytosine
• cytochrome 450
• cytosine deaminase
• fludarabine phosophate
• ganciclovir
• GDEPT
• gene-directed enzyme prodrug therapy
• nitroreductase
• prostate cancer
• purine nucleoside phosphorylase
• thymidine kinase

Notes