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Advances in adenovirus-mediated p53 cancer gene therapy.

AbstractINTRODUCTION:
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.
AuthorsHiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara
JournalExpert opinion on biological therapy (Expert Opin Biol Ther) Vol. 13 Issue 11 Pg. 1569-83 (Nov 2013) ISSN: 1744-7682 [Electronic] England
PMID24107178 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adenovirus E1A Proteins
  • Adenovirus E1B Proteins
  • MicroRNAs
  • Recombinant Fusion Proteins
  • Tumor Suppressor Protein p53
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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