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[p53: prospects for gene therapy of cancer]
Purpose:
To evaluate the prospects for cancer gene therapy through restoration of wild-type p53 (wt-p53) protein expression and/or function.
Design:
To review the most significant data reported in the literature with particular attention in dissecting the biological questions that are still open and need to be clarified to improve TP53-based gene therapy.
Results:
Considerable experimental evidence obtained in vitro and in vivo indicates that wt-p53 protein can suppress the transformed phenotype of several types of cancer in humans as well as other species. Wt-p53 protein suppress transformation by inducing different biological effects including maintenance of genomic stability, inhibition of cell proliferation, induction of apoptosis, differentiation or senescence. All these findings have rendered p53 a potential helpful target for therapy of many types of human cancers.
Conclusions:
Different experimental strategies based on i) TP53 gene-replacement, ii) restoration of wt-p53 activity, iii) replication of defective lytic viruses specifically in altered p53-expressing tumors, have given promising results in vitro and, in some cases also in vivo. At present, a few phase one clinical trials have been started for some of the gene-replacement strategies.
Insights
Restoring wild-type p53 (wt-p53) protein shows promise for cancer gene therapy by suppressing tumor growth. Ongoing research and early clinical trials explore TP53 gene replacement and activity restoration strategies.
Area of Science:
- Molecular biology
- Oncology
- Gene therapy
Context:
- The p53 tumor suppressor protein plays a critical role in maintaining genomic stability and preventing cancer development.
- Dysregulation or mutation of the TP53 gene is implicated in a significant percentage of human cancers.
- Restoring wild-type p53 (wt-p53) function is a promising strategy for cancer gene therapy.
Purpose:
- To evaluate the therapeutic potential of restoring wild-type p53 (wt-p53) protein expression and/or function in cancer gene therapy.
- To review current literature on TP53-based gene therapy, identifying open biological questions.
- To assess the efficacy of various TP53 gene therapy approaches.
Summary:
- Experimental evidence demonstrates that wt-p53 protein can suppress the transformed phenotype in various cancers by inducing apoptosis, inhibiting proliferation, and promoting differentiation or senescence.
- Multiple strategies, including TP53 gene replacement, restoration of wt-p53 activity, and oncolytic viruses targeting p53-altered tumors, have shown promising results in preclinical studies.
- Early-phase clinical trials are underway for some gene-replacement strategies, indicating progress in translating research findings.
Impact:
- Successful implementation of TP53-based gene therapy could offer novel treatment options for a wide range of human cancers.
- Further research into the biological mechanisms and optimization of delivery systems is crucial for advancing p53 gene therapy.
- The findings highlight the significance of p53 as a therapeutic target in oncology.