Use of p53 for therapy of human cancer

Autor: D. V. Kochetkov, Peter M. Chumakov, V. P. Almazov
Rok vydání: 2007
Předmět:
Zdroj: Molecular Biology. 41:863-877
ISSN: 1608-3245
0026-8933
Popis: Tumor suppressor p53 is the central component of a system maintaining the genetic stability of animal and human somatic cells. Its gene is inactivated in almost all human cancers, allowing a tumor cell to rapidly accumulate additional mutations and progress toward a more malignant phenotype. Yet tumor cells are most sensitive to the suppressor effect of p53 when its function is restored. Hence, restoration of the p53 function is an appealing strategy for anticancer therapy. Various mechanisms inactivate p53 in cancer, including point mutations resulting in synthesis of an inactive mutant protein, deletion of the total gene or its portion, damage to the genes involved in regulating the p53 activity, and defects in p53 target genes. In addition, oncogenic viruses code for the specialized proteins that modify the p53 function to ensure optimal replication of the virus genome. These viral proteins are crucial for virus-induced carcinogenesis, in particular, in 95% of cervical carcinoma cases in women. The approaches to p53 activity restoration depend to a great extent on the defect in p53-dependent signaling. Introduction of exogenous p53 is effective in some cases and is usually achieved with adenoviral vectors. The approaches under study are aimed at restoring the activity of mutant p53 or suppressing the viral inhibitors of p53. The review considers various schemes involving p53 in cancer therapy and prevention and discusses their potential efficacy and prospects of their clinical use.
Databáze: OpenAIRE
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