From gene therapy to virotherapy for ovarian cancer.
Ovarian cancer has the highest mortality of all cancers of the female reproductive system. Although progress in conventional therapies (surgery, chemotherapy and irradiation) has been achieved, the 5-year survival rate for patients with advanced stage ovarian cancer is still low. On this basis it is clear that there is a need for novel therapeutic paradigms. Targeted approaches are based on the increasing knowledge of the molecular basics of ovarian cancer. In this regard, gene therapy is a novel targeted approach for the treatment of ovarian cancer. However, current gene therapy delivery systems (viral and non-viral vectors) have to address the issues of inefficient transduction of target ovarian cancer cells and/or ectopic non-target delivery with attendant toxicity. Of note, the limited tumor transduction associated with current gene therapy interventions is due, in large part, to the fact that the employed vectors have been replication-incompetent. In this regard, human clinical trials have shown that the approach of replication-incompetent vectors has yet to succeed in ovarian cancer patients. In contrast, replication-competent viruses offer a method to achieve efficient tumor cell oncolysis (virotherapy) in ovarian cancer. Thus, in this very promising approach of virotherapy the replicating virus itself is the anti-cancer agent. This review discusses the concepts of gene therapy and virotherapy as novel targeted therapeutic approaches for the treatment of ovarian cancer.
Stoff-Khalili
M A
MA
Division of Human Gene Therapy, Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Dall
P
P
Curiel
D T
DT
D000230:Adenocarcinoma / Q000235:genetics / Q000628:therapy; D000256:Adenoviridae / Q000235:genetics; D002986:Clinical Trials as Topic; D005260:Female; D018014:Gene Transfer Techniques; D005814:Genes, Viral; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D014779:Virus Replication; D014780:Viruses / Q000235:genetics* / Q000276:immunology*