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Updated: Aug 8, 2026

Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Adenovirus-mediated p53 tumor suppressor gene therapy of osteosarcoma
Vladimir V Ternovoi1, David T Curiel, Bruce F Smith
1Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
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.
Insights
Gene therapy using p53, a tumor suppressor, shows promise for osteosarcoma (OS) treatment. Current adenovirus vectors need improvement for better efficacy in clinical applications against this challenging cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Osteosarcoma (OS) treatment outcomes remain poor despite conventional therapies.
- Tumor suppressor gene therapy, specifically p53 gene replacement, offers a novel therapeutic avenue.
- Previous p53 gene therapy trials faced challenges with vector efficacy and in vivo activity.
Purpose of the Study:
- To review the current status of adenovirus-mediated p53 gene therapy for osteosarcoma.
- To discuss advancements in understanding p53's role and chemoresistant OS biology.
- To explore improved tumor targeting strategies using adenoviral vectors.
Main Methods:
- Review of existing literature on p53 gene therapy for osteosarcoma.
- Analysis of clinical trial data regarding vector efficacy and p53 activity.
- Examination of molecular mechanisms in chemoresistant OS and adenoviral vector technology.
Main Results:
- Wild-type p53 introduction can be lethal to cancer cells in vitro.
- Clinical trials demonstrated limited success due to insufficient vector efficacy and low in vivo proapoptotic activity.
- Recent advancements offer potential for enhanced tumor targeting and therapeutic outcomes.
Conclusions:
- Adenovirus-mediated p53 gene therapy holds potential for osteosarcoma treatment.
- Further research is needed to optimize vectors and enhance p53's therapeutic efficacy.
- Future investigations should focus on improving tumor targeting and overcoming chemoresistance.
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