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p53 Replacement Therapy for Cancer

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Current Strategies in Cancer Gene Therapy

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 209))

Abstract

Tumor suppressor gene (TSG) replacement therapy that involves various delivery systems is emerging as a promising antitumor strategy because malignant tumors develop through genetic alterations in TSGs. The most potent therapeutic TSG for tumor suppression is the multifunctional transcription factor p53 gene that regulates diverse cellular phenomena such as cell cycle arrest, senescence, apoptosis, and autophagy. Since the p53 gene is frequently inactivated by aberrant genetic regulation in human cancers, p53 replacement therapy is widely and frequently used as a potent antitumor strategy to restore wild-type p53 function in the p53-inactivated tumors. This chapter focuses on four types of p53 transfer systems: cationic liposome–DNA plasmid complexes, a replication-deficient adenovirus vector, a replication-competent adenovirus vector, and a protein transduction system. Moreover, we discuss recent advances in our understanding of the molecular basis of the p53-mediated cell death signaling pathway and therapeutic methods for enhancing tumor cell death and induction of bystander effects within tumor tissues in p53 replacement therapy. Exploration of the molecular mechanism underlying the p53-mediated tumor-suppressive network system and development of an effective strategy for enhancing p53-mediated cell death signaling pathways would lead to an improvement in the clinical outcome of patients with p53-inactivated cancers.

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Abbreviations

TSG:

Tumor suppressor gene

MDM2:

Mouse double minute 2

DRAM:

Damage-regulated autophagy modulator

hTERT:

human telomerase reverse transcriptase

CAR:

Coxsackie and adenovirus receptors

DCs:

Dendritic cells

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Acknowledgments

This study was supported by grants from the Ministry of Health, Labour, and Welfare of Japan and from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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Authors and Affiliations

  1. Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, 700-8558, Japan

    Hiroshi Tazawa

  2. Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan

    Hiroshi Tazawa, Shunsuke Kagawa & Toshiyoshi Fujiwara

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  1. Hiroshi Tazawa
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  2. Shunsuke Kagawa
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  3. Toshiyoshi Fujiwara
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Correspondence to Toshiyoshi Fujiwara .

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Editors and Affiliations

  1. Department of Translational Oncology, Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Berlin, Germany

    Wolfgang Walther

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Tazawa, H., Kagawa, S., Fujiwara, T. (2016). p53 Replacement Therapy for Cancer. In: Walther, W. (eds) Current Strategies in Cancer Gene Therapy. Recent Results in Cancer Research, vol 209. Springer, Cham. https://doi.org/10.1007/978-3-319-42934-2_1

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  • DOI: https://doi.org/10.1007/978-3-319-42934-2_1

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