Adenovirus-mediated p53 tumor suppressor gene therapy of osteosarcoma

Vladimir V. Ternovoi, David T. Curiel, Bruce F. Smith, Gene P. Siegal

Research output: Contribution to journalReview article

26 Scopus citations

Abstract

The clinical outcome for osteosarcoma (OS) remains discouraging despite efforts to optimize treatment using conventional modalities including surgery, radiotherapy and chemotherapy. Novel therapeutic approaches based on our expanding understanding of the mechanisms of tumor cell killing have the potential to alter this situation. Tumor suppressor gene therapy aims to restore the function of a tumor suppressor gene lost or functionally inactivated in cancer cells. One such molecule, the p53 tumor suppressor gene plays a critical role in safeguarding the integrity of the genome and preventing tumorigenesis. Introduction of wild-type (wt) p53 into transformed cells has been shown to be lethal for most cancer cells in vitro, but clinical trials of p53 gene replacement have had limited success. Analysis of these clinical trials highlighted the insufficient efficacy of current vectors and low proapoptotic activity of wt p53 as a single agent in vivo. In this review, a contemporary summarization of the current status of adenovirus-mediated p53 gene therapy of OS is presented. Advancement in our understanding of p53 tumor suppressor activity, the molecular biology of chemoresistant OS, and recent advances in tumor targeting with adenoviral vectors are also addressed. Based on these parameters, prospects for future investigations are proposed.

Original languageEnglish
Pages (from-to)748-766
Number of pages19
JournalLaboratory Investigation
Volume86
Issue number8
DOIs
StatePublished - Aug 29 2006
Externally publishedYes

Keywords

  • Adenovirus
  • Gene therapy
  • Osteosarcoma
  • Tumor suppressor
  • p53

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