engleski

Adenovirus Mediated p53 or p21WAF1/CIP1 Gene Transfer and its Impact on Cancer Therapy

One of the new approaches to therapy is to restore apoptotic potential by gene therapy. Among the most important genes that regulate the apoptotic program is the p53 gene – so called "a master regulator". Based on this, the gene replacement therapy with wtp53, mainly using adenoviral vectors, provides an attractive strategy to cancer treatment, and the first gene-based therapeutic – Gendicine (adenoviral vector bearing p53 gene) has been approved in China, in 2003. Still, while the majority of the data support a role for mutated p53 in reducing chemosensitvity, the other indicate either no correlation or even increased sensitivity to chemotherapeutic agents resulting in much experimental work tending to elucidate mechanisms for these contradictory results. Moreover, the cell-cycle regulator p21WAF1/CIP1 is one of the most important p53-regulated genes. Its role in the cell-response to therapy has become more and more complex and controversial since its discovery. Its induction is essential for the onset of cell cycle arrest in damage response and cell senescence and therefore implicated in response to many cancer treatments. However, its role in different forms of drug-induced cell death is not fully understood ; it could be either pro-, or anti- apoptotic and it highly depends on cell type and cellular context. Using adenoviruses for the introduction of p53 and p21WAF1/CIP1 genes to tumor cells, we are studying their roles and potentials of their exploitation in tumor therapy and some of our recent findings will be presented.

adenoviruses; chemotrepary; gene therapy; p53; p21

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