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Weill Cornell team identifies potential new cancer drug target

NEW YORK (June 20, 2007) -- Research led by scientists at Weill Cornell Medical College has uncovered two new potential points of vulnerability on a key cancer-promoting protein, called XIAP. Drugs that target either of these activities could help push cancer cells back into a more regular programmed cell death and thereby reduce or eliminate tumors.

These findings were published in the June 8 issue of Molecular Cell by Dr. Hao Wu, a professor in the Department of Biochemistry of Weill Cornell, and her team.

Experts know that cancers spread in two separate ways -- by the uncontrolled proliferation of cells, and by their refusal to undergo normal, healthy, programmed cell death, or "apoptosis."

In many cancers, dysfunction in a biochemical cascade called the NF-kappa B pathway causes tumor cells to sidestep apoptosis and become dangerously immortal.

"So, drug development aimed at short-circuiting NF-kappa B has become very hot in the past few years," Dr. Wu says.

Her team focused on a particular protein involved in the NF-kappa B pathway called the "X-linked inhibitor of apoptosis" (XIAP). Scientists had already discovered that XIAP thwarts the apoptotic impulse by putting the brakes on key enzymes called caspases. XIAP is also known to be highly active in cancer cells, but it is found in relatively low levels in healthy cells. How XIAP inhibits caspases is known, but how XIAP induces NF-kappa B activation is entirely unclear.

"We wondered if we could find out how XIAP induces the NF-kappa B pathway," explains lead researcher Dr. Miao Lu, a postdoctoral fellow of biochemistry at Weill Cornell.

In their experiments, the researchers used a variety of cutting-edge techniques, including X-ray crystallography, to track changes in the structure and activity of XIAP and the molecules it interacts with in cells.

"We discovered that XIAP interacts with the NF-kappa B cycle in two distinct wa
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Contact: Andrew Klein
ank2017@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
21-Jun-2007


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