Article: Discovery about obesity drug helping scientists develop new cancer treatments

Article: http://www.mooshee.com/article-29961026.htm
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Based on their surprising discovery that an obesity drug can kill cancer
cells, scientists at Wake Forest University School of Medicine have made a
new finding about the drug's effects and are working to design more potent
cancer treatments.

Published online today in Nature Structural and Molecular Biology, the study
is the first to report how the drug orlistat (Xenical® or Alli®) binds and
interacts with a protein found in tumor cells. The drug blocks the protein's
function and causes cell death.

The project started five years ago when Steven Kridel, Ph.D., an assistant
professor in the Department of Cancer Biology, analyzed prostate cancer
cells to see which enzymes were expressed at high levels. His hope was that
treatments to inhibit those enzymes could also stop tumor growth.

"We found that a protein known as fatty acid synthase is expressed at high
levels in prostate tumor cells, and is fairly absent in normal cells," said
Kridel.

Other research has shown that the protein is found in many tumor cells
including breast, colon, ovarian, liver, lung and brain.

"High levels of fatty acid synthase correlate with a poor prognosis so it is
a great treatment target," said Kridel. "This makes an exciting treatment
target because theoretically you don't have to worry about harming nearby
healthy tissue."

Unfortunately, orlistat itself cannot be used as a cancer treatment because,
while it can kill cancer cells in the laboratory, in humans it is designed
to act only in the digestive tract.

"Understanding this drug-protein interaction is essential for designing new
drugs," said W. Todd Lowther, Ph.D., an assistant professor in the
Department of Biochemistry. "We've used a technique known as X-ray
crystallography and now have a three-dimensional snapshot of the drug
interacting with the protein."

"Our goal is to develop an orlistat-like drug that can get into the
bloodstream and go to the site of a tumor," said Lowther.

Once they developed the three-dimensional map of the interaction, Lowther
and Kridel began screening hundreds of thousands of compounds to identify
those that interact with cancer cells in the same way as orlistat. They have
narrowed the list of possibilities down to a dozen and will now work to
optimize the compounds in hopes of creating potent cancer treatments. The
drugs will first be tested in animals and then in human cancer patients.

Fatty acid synthase is also found in fat cells, which suggests that if the
scientists are successful in developing an anti-cancer drug, it could also
be an effective obesity drug.

"You might have the same drug for treating a cancer patient as an obese
patient," said Lowther.

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