title: Stem cell based cancer gene therapy.
abstract: The attractiveness of prodrug cancer gene therapy by stem cells targeted to tumors lies in activating the prodrug directly within the tumor mass, thus avoiding systemic toxicity. Suicide gene therapy using genetically engineered mesenchymal stem cells has the advantage of being safe, because prodrug administration not only eliminates tumor cells but consequently kills the more resistant therapeutic stem cells as well. This review provides an explanation of the stem cell-targeted prodrug cancer gene therapy principle, with focus on the choice of prodrug, properties of bone marrow and adipose tissue-derived mesenchymal stem and neural stem cells as well as the mechanisms of their tumor homing ability. Therapeutic achievements of the cytosine deaminase/5-fluorocytosine prodrug system and Herpes simplex virus thymidine kinase/ganciclovir are discussed. In addition, delivery of immunostimulatory cytokines, apoptosis inducing genes, nanoparticles and antiangiogenic proteins by stem cells to tumors and metastases is discussed as a promising approach for antitumor therapy. Combinations of traditional, targeted and stem cell-directed gene therapy could significantly advance the treatment of cancer.
authors.affiliation: Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Marina
authors.initials: M
authors.lastname: Cihova
authors.forename: Veronika
authors.initials: V
authors.lastname: Altanerova
authors.forename: Cestmir
authors.initials: C
authors.lastname: Altaner
mesh_terms: D053687:Adult Stem Cells / Q000201:enzymology / Q000637:transplantation; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D002465:Cell Movement; D002478:Cells, Cultured / Q000201:enzymology / Q000637:transplantation; D003131:Combined Modality Therapy; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000628:therapy*; D058953:Neural Stem Cells / Q000201:enzymology / Q000637:transplantation; D011355:Prodrugs / Q000493:pharmacokinetics / Q000627:therapeutic use; D018139:Simplexvirus / Q000201:enzymology; D033581:Stem Cell Transplantation; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; D014764:Viral Proteins; D013937:Thymidine Kinase; D043525:Cytosine Deaminase