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廣島 健三
Department Other, Other Position |
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| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | Gene therapy for malignant mesothelioma: Current prospects and challenges. |
| Journal | Formal name：Cancer gene therapy Abbreviation：Cancer Gene Ther ISSN code：1476-5500(Electronic)0929-1903(Linking) |
| Volume, Issue, Page | 20(3),pp.150-156 |
| Author and coauthor | Tagawa M†, Tada Y, Shimada H, Hiroshima K |
| Authorship | Last author |
| Publication date | 2013/03 |
| Summary | Malignant mesothelioma, developed in the thoracic cavity, is resistant to current treatments. Suppression of the local tumor growth is beneficial to the patients since mesothelioma infrequently metastasizes to extrapleural organs. A majority of the tumors have a homologous genetic deletion at the INK4A/ARF locus that includes the p14(ARF) and the p16(INK4A) genes, and the genetic defect results in an inactivation of the p53-mediated pathways and in progression of cell cycle through pRb phosphorylation. Preclinical studies targeting the genetic abnormality with adenoviruses showed that restoration of the p53 pathways induced pRb dephosphorylation and subsequently produced anti-tumor effects. A number of preclinical studies with different genes and vector systems demonstrated the therapeutic efficacy and raised the possibility of gene therapy in clinical settings. An intrapleural administration of vectors has several advantages in transducing pleural mesothelioma but activates rapid antibody production which impedes further gene expression. There have been several clinical studies conducted for mesothelioma and these trials showed the feasibility of intrapleural administrations of adenovirus vectors. In this review we summarize major preclinical and clinical gene therapy for mesothelioma, and discuss the advantages of gene therapy in the context of stimulating host immune systems. Accumulating clinical data suggest that an intrapleural administration of viral vectors has distinct aspects which are not observed in other administration routes.Cancer Gene Therapy advance online publication, 8 February 2013; doi:10.1038/cgt.2013.1. |
| DOI | 10.1038/cgt.2013.1 |
| Document No. | 23392201 |