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Gene therapy for malignant mesothelioma: Current prospects and challenges

Cancer Gene Therapy volume 20, pages 150–156 (2013)Cite this article

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Abstract

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 p14ARF and the p16INK4A 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.

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Acknowledgements

This work was partly supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan, and a Grant-in-aid from the Nichias Corporation.

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Authors and Affiliations

  1. Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan

    M Tagawa

  2. Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan

    M Tagawa

  3. Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Y Tada

  4. Department of Surgery, School of Medicine, Toho University, Tokyo, Japan

    H Shimada

  5. Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan

    K Hiroshima

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Correspondence to M Tagawa.

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Tagawa, M., Tada, Y., Shimada, H. et al. Gene therapy for malignant mesothelioma: Current prospects and challenges. Cancer Gene Ther 20, 150–156 (2013). https://doi.org/10.1038/cgt.2013.1

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