Targeting oncogenes to improve XXXX chemotherapy.

@entity1 @entity2353 @entity0 @entity5 @entity517 @entity136
Despite recent advances in treatment, @entity0 remains a serious health threat for @entity1 . Traditional chemotherapies are limited by a lack of specificity for @entity5 cells and the cell cycle dependence of many chemotherapeutic agents. Here we report a novel strategy to help overcome these limitations. Using triplex-forming oligonucleotides (TFOs) to direct DNA damage site-specifically to oncogenes overexpressed in @entity1 @entity0 cells, we show that the effectiveness of the anticancer @entity2353 analogue @entity136 can be improved significantly. TFOs targeted to the promoter region of @entity517 directly inhibited gene expression by approximately 40%. When used in combination, specific TFOs increased the incorporation of @entity136 at the targeted site approximately 4-fold, presumably due to induction of replication-independent DNA synthesis. Cells treated with TFOs and @entity136 in combination showed a reduction in both cell survival and capacity for anchorage-independent growth (approximately 19% of untreated cells). This combination affected the tumorigenic potential of these @entity5 cells to a significantly greater extent than either treatment alone. This novel strategy may be used to increase the range of effectiveness of antitumor nucleosides in any @entity5 which overexpresses a targetable oncogene. Multifaceted chemotherapeutic approaches such as this, coupled with triplex-directed gene targeting, may lead to more than incremental improvements in nonsurgical treatment of @entity0 .
