Abstract | INTRODUCTION: The tumor suppressor p53 gene regulates diverse cellular processes, such as cell-cycle arrest, senescence, apoptosis and autophagy, and it is frequently inactivated by genetic alterations in ∼ 50% of all types of human cancers. To restore wild-type p53 function in p53-inactivated tumors, adenovirus-mediated p53 gene therapy has been developed as a promising antitumor strategy in preclinical experiments and clinical studies. AREAS COVERED: This review focuses on the clinical relevance of replication-deficient adenovirus vectors that carry the wild-type p53 gene (Ad-p53; Advexin, Gendicine and SCH-58500) in clinical studies of patients with various cancers and the future perspectives regarding conditionally replicating adenovirus vectors expressing the wild-type p53 gene (CRAd-p53; AdDelta24-p53, SG600-p53, OBP-702) in preclinical experiments. Moreover, the recent advances in our understanding of the molecular basis for the p53-mediated tumor suppression network induced by Ad-p53 and CRAd-p53 vectors and the combination therapies for promoting the therapeutic potential of adenovirus-mediated p53 gene therapy are discussed. EXPERT OPINION: Exploration of the molecular mechanism underlying the p53-mediated tumor suppression network and the effective strategy for enhancing the p53-mediated cell death signaling pathway would provide novel insights into the improvement of clinical outcome in p53-based cancer gene therapy.
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Authors | Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara |
Journal | Expert opinion on biological therapy
(Expert Opin Biol Ther)
Vol. 13
Issue 11
Pg. 1569-83
(Nov 2013)
ISSN: 1744-7682 [Electronic] England |
PMID | 24107178
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adenovirus E1A Proteins
- Adenovirus E1B Proteins
- MicroRNAs
- Recombinant Fusion Proteins
- Tumor Suppressor Protein p53
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Topics |
- Adenoviridae
(genetics)
- Adenovirus E1A Proteins
(genetics, physiology)
- Adenovirus E1B Proteins
(genetics, physiology)
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Apoptosis
- Bystander Effect
- Clinical Trials as Topic
- Combined Modality Therapy
- Female
- Gene Expression Regulation, Neoplastic
- Gene Expression Regulation, Viral
- Genes, p53
- Genetic Therapy
(methods)
- Genetic Vectors
(administration & dosage, genetics, therapeutic use)
- Humans
- Injections, Intralesional
- Male
- MicroRNAs
(genetics, physiology)
- Neoplasms
(drug therapy, genetics, radiotherapy, therapy)
- Recombinant Fusion Proteins
(genetics, metabolism)
- Signal Transduction
- Transgenes
- Tumor Suppressor Protein p53
(administration & dosage, deficiency, genetics, physiology)
- Virus Replication
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