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Turning a painkiller into a cancer killer
Date:6/14/2010

LA JOLLA, Calif., June 15, 2010 Without knowing exactly why, scientists have long observed that people who regularly take non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin have lower incidences of certain types of cancer. Now, in a study appearing in Cancer Cell on June 15, investigators at Sanford-Burnham Medical Research Institute (Sanford-Burnham) and their colleagues have figured out how one NSAID, called Sulindac, inhibits tumor growth. The study reveals that Sulindac shuts down cancer cell growth and initiates cell death by binding to nuclear receptor RXRα, a protein that receives a signal and carries it into the nucleus to turn genes on or off.

"Nuclear receptors are excellent targets for drug development," explained Xiao-kun Zhang, Ph.D., professor at Sanford-Burnham and senior author of the study. "Thirteen percent of existing drugs target nuclear receptors, even though the mechanism of action is not always clear."

RXRα normally suppresses tumors, but many types of cancer cells produce a truncated form of this nuclear receptor that does just the opposite. This study showed that shortened RXRα enhances tumor growth by stimulating other proteins that help cancer cells survive. Luckily, the researchers also found that Sulindac can be used to combat this deviant RXRα by switching off its pro-survival function and turning on apoptosis, a process that tells cells to self-destruct.

Sulindac is currently prescribed for the treatment of pain and fever, and to help relieve symptoms of arthritis. The current study demonstrates a new application for Sulindac as a potential anti-cancer treatment that targets truncated RXRα protein in tumors. However, some NSAIDs have gotten a lot of bad press for their potentially dangerous cardiovascular side effects. To overcome this limitation, the researchers tweaked Sulindac, creating a new version of the drug now called K-80003 that both decreases negativ
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Contact: Josh Baxt
jbaxt@sanfordburnham.org
858-795-5236
Sanford-Burnham Medical Research Institute
Source:Eurekalert

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