(Philadelphia, PA) Researchers at the Leonard and Madlyn Abramson Family Cancer Research Institute at the University of Pennsylvania have found a second way by which chemotherapeutic agents can kill cancer cells. The finding which will appear online and ahead of print in the June 1st edition of the journal Genes & Development represents an important advance in understanding how and why some cancer cells die and others do not in response to existing chemotherapy. The results suggest the possibility that targeted therapies can be developed which will force cancer cells to die before they can grow into tumors.

"This finding shows, for the first time, that cancer cells are unusually sensitive to dying by necrosis, when their ability to metabolize glucose is blocked," said Craig Thompson, MD, Principal Investigator of the study and Scientific Director of the Abramson Family Cancer Research Institute (AFCRI). "Up until now, research has focused on finding ways to program cancer cells to die through apoptosis a very regulated, orderly form of cell death that does not trigger an immune response. Now, we know that cancer cells can be forced to die, suddenly, through necrosis. If we can harness this method, which does trigger an immune response, then, the door will be opened to a whole new and less toxic way to treat cancer."

Despite long-term use, the action of chemotherapeutic agents to kill and stop the growth of cancer cells is not well understood. The agents have proven to be effective treatments even for tumors lacking the genes considered essential for apoptosis, but the precise cellular mechanism for this has remained unexplained up until now.

To study this issue, the researchers created mouse cells that were unable to die by apoptosis. The cells were engineered to be deficient in either the tumor suppressor gene p53, the most commonly mutated gene in human cancer, or two key proteins essential for the execution of apoptotic cell death,
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Contact: David March
david.march@uphs.upenn.edu
215-615-3353
University of Pennsylvania School of Medicine
13-May-2004

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