[The use of p53 as a tool for human cancer therapy]

The p53 tumor suppressor is a central component of a system that reinforces genetic stability of somatic cells in animals and humans. Inactivation of this gene occurs virtually in every cancer case, which eliminates results in further rapid accumulation of additional mutations leading to progression of a cancer cell toward more malignant phenotype. The mechanisms of p53 inhibition in cancer include point mutations leading to accumulation of inactive protein, deletion of the whole gene, or its portion, alteration in the genes involved in regulation of activity of p53, and defects in the genes controlled by p53. In addition, oncogenic viruses encode specialized proteins that are entitled to modify p53 functions in order to provide optimal condition for replication of viral genome. These viral proteins play central role in viral carcinogenesis, including 95% of cases of cervical carcinoma in women. The approacheas to restoration of p53 activity depend on particular type of alteration within the p53 pathway. In some cases an effective mean would be introduction of exogenous p53, particularly with the use of adenoviral vectors. There are also approaches in development that target reactivation of mutant proteins, or suppress natural inhibitors of p53. The review summarizes various schemes for therapy and prevention of cancer that are based on our knowledge of the p53 gene functions. Potential usefulness of the approaches for practical applications is discussed.