NCI researchers have developed a novel method in mice of delivering genes to cancer cells, that when expressed, promote cell death. These genes, known as suicide genes, cause a cell to kill itself through a process known as apoptosis. The new technique uses the survivin gene promoter to express the suicide gene and induce apoptosis in cancer cells. This method of gene delivery effectively targeted tumor cells with a minimum effect on normal cells.

Tumor specific promoters, such as the survivin promoter, can be used to target genes to cancer cells, but the expression of the protein product is often suboptimal. The NCI team devised a way to overcome this problem by developing a more potent suicide gene. They created a mutation in the area of the suicide gene bax that regulates its apoptotic activity. Laboratory studies showed that when expressed via the survivin promoter, the mutant bax gene had increased cell killing activity in a variety of cancer cell types compared to the unmutated form of the gene. The researchers also found that the survivin promoter-driven mutant bax was minimally toxic to normal human skin cells. When injected into tumors of mice, the gene induced more than 60 percent of the cancer cells in the tumor tissue to die and slowed tumor growth significantly. The results of this study appeared online October 9, 2009, in Cancer Gene Therapy.

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