Wednesday November 25 2009 | Biotechnology feed | All feeds
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Wednesday November 25 2009 | Biotechnology feed | All feeds
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Histone deacetylase inhibitors as pro-apoptotic candidates A variety of chemotherapies are available to oncologists and these generally reduce the rate of tumor progression. However intrinsic or acquired tumor-mediated drug resistance is a major clinical obstacle that can result in the lack of tumor responsiveness in patients undergoing treatment. Drug resistance is in part due to active efflux transporters such as p-glycoprotein which pump chemotherapeutic agents out of the cell and also regulate caspase activity. Consequently the development of inhibitors of this protein or of chemotherapies able to bypass drug resistance represents an active area of the pharmaceutical industry. Histone deacetylase (HDA) inhibitors represent a therapeutic class holding considerable potential for the treatment of cancer. This potential has been further boosted by recent studies demonstrating that the chemotherapeutic hybrid polar compound suberoylanilide hydroxamic acid (SAHA), a prototype HDA inhibitor induced equivalent death in p-glycoprotein-positive cells compared with p-glycoprotein-negative cells. Cell death was marked by the caspase-independent release of cytochrome c, reactive oxygen species (ROS) production and Bid cleavage that was not affected by p-glycoprotein expression. This data demonstrates that SAHA may be of value for the treatment of drug resistant cancers. Link to journal abstract:
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