Novel gene-directed enzyme prodrug therapies against prostate cancer.
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.
Russell
Pamela J
PJ
Oncology Research Centre, Prince of Wales Hospital Sydney, Level 2, Clinical Sciences Building, Barker Street, Randwick, NSW 2031, Australia. p.Russell@unsw.edu.au
Khatri
Aparajita
A
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D024201:Bystander Effect; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D005437:Flucytosine / Q000378:metabolism / Q000627:therapeutic use; D015774:Ganciclovir / Q000378:metabolism / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000639:trends*; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D011355:Prodrugs / Q000378:metabolism / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D011355:Prodrugs; D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System; D005437:Flucytosine; D013937:Thymidine Kinase; D043525:Cytosine Deaminase; D015774:Ganciclovir