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Advances in adenovirus-mediated p53 cancer gene therapy
Hiroshi Tazawa1, Shunsuke Kagawa, Toshiyoshi Fujiwara
1Okayama University Hospital, Center for Innovative Clinical Medicine , Okayama 700-8558 , Japan.
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.
Insights
Adenovirus-mediated p53 gene therapy shows promise for treating cancers with p53 gene inactivation. Further research into p53
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- The tumor suppressor p53 gene is crucial for regulating cell processes and is inactivated in about 50% of human cancers.
- Adenovirus-mediated p53 gene therapy aims to restore wild-type p53 function in tumors with p53 inactivation.
Purpose of the Study:
- This review examines the clinical relevance of replication-deficient adenovirus vectors carrying the wild-type p53 gene (Ad-p53) in cancer patients.
- It also explores future perspectives for conditionally replicating adenovirus vectors expressing wild-type p53 (CRAd-p53) in preclinical settings.
Main Methods:
- The review analyzes clinical studies of Ad-p53 vectors (Advexin, Gendicine, SCH-58500) in various cancers.
- It discusses preclinical data for CRAd-p53 vectors (AdDelta24-p53, SG600-p53, OBP-702).
- Advances in understanding the p53-mediated tumor suppression network and combination therapies are also covered.
Main Results:
- Clinical studies have evaluated Ad-p53 vectors in patients with different cancer types.
- Preclinical experiments are investigating CRAd-p53 vectors for their therapeutic potential.
- Understanding the molecular basis of p53-mediated tumor suppression is advancing.
Conclusions:
- Further exploration of the p53-mediated tumor suppression network is needed.
- Developing strategies to enhance p53-mediated cell death signaling can improve outcomes.
- These insights are vital for advancing p53-based cancer gene therapy.
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