nce imaging technology has provided a breakthrough that allows scientists to examine the size of a tumor in living mice with high sensitivity," says El-Deiry. "Since the reporter gene is always on and only in the tumor cell, it's essentially measuring tumor volume. Using the reporter gene along with the KILLER/DR5 silencer, we show for the first time that when we turn off KILLER/DR5, we get bigger tumors."

While the beacon or beacon cocktails have the potential to be used in the clinic to detect mutations in cancer cells or the activation of genes that predict therapeutic response, the major advance with the bioluminescence imaging is in accelerating preclinical drug development. The gene silencing allows precise molecular characterization of targets that are relevant for therapeutic response while the imaging allows non-invasive assessment of drug activity towards implanted tumors. This approach saves time and money because it is possible to see the effects of drugs in living mice without sacrificing them and it also requires fewer mice in experiments.

Because the KILLER/DR5 receptor is involved in the process of cell death by chemotherapy, El-Deiry is also gaining insight into which drugs use it and which drugs work by other mechanisms. "This is important because to maximize tumor killing and to attempt to bypass or reverse resistance to chemotherapy, we need to harness all the ways cancer cells can be killed," he says.

The KILLER/DR5 receptor is engaged by a therapeutic agent currently being developed called TRAIL (Tumor necrosis factor-Related Apoptosis Inducing Ligand). TRAIL is produced normally by natural killer cells and controls tumor spread by binding to a tumor's death-inducing receptor KILLER/DR5. "However, in cancer patients with suppressed immunity and for reasons we still don't understand, there isn't enough TRAIL being produced or effectively delivered by the natural killer cells at the site of tumors and so tumors are not s
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
1-Dec-2004

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