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Molecular tailoring of chemotherapy with novel imaging techniques

(Philadelphia, PA) Researchers at the Abramson Cancer Center of the University of Pennsylvania are applying a host of imaging techniques to develop better ways to look noninvasively at the molecular characteristics of tumors. The experiments, now in human cell cultures and mouse models, are aimed at better forecasting early response to chemotherapy so that treatment choices can be adjusted.

"Right now in cancer therapy, with the exception of relatively uncommon examples of cancers for which we have tumor markers, we don't have reliable ways of predicting who is going to respond early on to chemotherapy," says Wafik El-Deiry, MD, PhD, Associate Professor, Departments of Medicine, Genetics, and Pharmacology. "Currently cancer patients get their chemo and you can't tell if they're responding for several weeks. We need to have tests that will tell us if patients are going to respond to the chemo or the radiation soon after it's first given, and whether these responses are going to last."

Two recent papers in Cancer Biology & Therapy and Cancer Research describe the work of the El-Deiry laboratory. One approach is to use a molecular beacon, a molecule that can be activated within cells due to a specific context, such as in this case, the response to chemotherapy. The beacon recognizes a characteristic change in chemo-treated tumor cells, physically opens up and fluoresces, which can then be measured. "The beacon goes right into the living cell and if it opens up, emitting fluorescence, we can detect the glow," says El-Deiry.

Human lung-cancer cells were treated with the chemotherapeutic agent doxorubicin (Adriamycin), which causes cellular DNA damage. Doxorubicin works through the tumor suppressor protein p53, which ultimately kills many types of cancer cells. "We engineered a molecular beacon to detect expression of a gene called p21, that is turned on directly by p53 when cells are exposed to Doxorubicin," says El-Deiry.

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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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