Advances in adenovirus-mediated p53 cancer gene therapy

Expert Opin Biol Ther. 2013 Nov;13(11):1569-83. doi: 10.1517/14712598.2013.845662.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Adenovirus E1A Proteins / genetics
  • Adenovirus E1A Proteins / physiology
  • Adenovirus E1B Proteins / genetics
  • Adenovirus E1B Proteins / 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
  • Genetic Vectors / genetics
  • Genetic Vectors / therapeutic use*
  • Humans
  • Injections, Intralesional
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / physiology
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / radiotherapy
  • Neoplasms / therapy*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Transgenes
  • Tumor Suppressor Protein p53 / administration & dosage
  • Tumor Suppressor Protein p53 / deficiency
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology
  • Virus Replication


  • Adenovirus E1A Proteins
  • Adenovirus E1B Proteins
  • MicroRNAs
  • Recombinant Fusion Proteins
  • Tumor Suppressor Protein p53