Suicide gene therapy in cancer: Where do we stand now?

• Published in: Cancer letters Vol. 324; no. 2; pp. 160 - 170
• Main Authors: Duarte, Sónia, Carle, Georges, Faneca, Henrique, Lima, Maria C. Pedroso de, Pierrefite-Carle, Valérie
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 28.11.2012; Elsevier Limited; Elsevier
• Subjects: Animals; Antineoplastic Agents; Antineoplastic Agents - metabolism; Antineoplastic Agents - therapeutic use; Apoptosis; Biochemistry, Molecular Biology; Bystander Effect; Cancer; Cancer therapies; Clinical trials; Combined strategies; Cytotoxicity; Deoxyribonucleic acid; DNA; drugs; Enzymes; Free radicals; Gene Therapy; Gene Transfer Techniques; Genes, Transgenic, Suicide; Genetic Therapy - methods; Hematology, Oncology and Palliative Medicine; Humans; in vivo studies; Kinases; Life Sciences; Neoplasms; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Neoplasms - therapy; Neoplastic Stem Cells; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - pathology; patients; Prodrugs; Prodrugs - metabolism; Prodrugs - therapeutic use; Prostate cancer; stem cells; Suicide gene therapy; suicide genes; Suicides & suicide attempts; Tumors; Chol; Combined strategies; herpes simplex virus thymidine kinase; thymidine kinase; Bystander effect; 5-FC; AMSCs; HSV-tk; MSCs; natural killer; cholesterol; cancer stem cells; CSCs; PSA; CD; uracil phosphoribosyltransferase; neural stem cells; cytosine deaminase; GvHD; ganciclovir; 5-fluorouracil; Suicide gene therapy; NSCs; mesenchymal stem cells; TK; UPRT; DOTAP; GCV; adipose tissue mesenchymal stromal cells; 5-fluorocytosine; NK; 1,2-dioleoyl-3-(trimethylammonium) propane; graft-versus-host disease; 5-FU; prostate-specific antigen; Cancer
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2012.05.023

Suicide gene therapy is based on the introduction into tumor cells of a viral or a bacterial gene, which allows the conversion of a non-toxic compound into a lethal drug. Although suicide gene therapy has been successfully used in a large number of in vitro and in vivo studies, its application to cancer patients has not reached the desirable clinical significance. However, recent reports on pre-clinical cancer models demonstrate the huge potential of this strategy when used in combination with new therapeutic approaches. In this review, we summarize the different suicide gene systems and gene delivery vectors addressed to cancer, with particular emphasis on recently developed systems and associated bystander effects. In addition, we review the different strategies that have been used in combination with suicide gene therapy and provide some insights into the future directions of this approach, particularly towards cancer stem cell eradication.