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Vitamin A analog is a potential lung cancer preventative with few side effects

nown lung carcinogens.

"Seeing this magnitude of response in such a strongly susceptible mouse suggests bexarotene is a potentially viable lung cancer prevention candidate," You says.

Vitamin A analogs called retinoids have been studied for several years as potential chemotherapeutic agents because they help regulate cell division, growth, differentiation and proliferation. A new class of these vitamin A relatives has been created that includes bexarotene. These substances are called the rexinoids, so named because they are attracted to a molecule on cell surfaces called RXR.

Rexinoids tend to be much less toxic than retinoids, and among them bexarotene has so far shown the most promise as a chemopreventive medicine. However, although it causes far fewer side effects, bexarotene does have the effect of increasing blood lipid levels in many patients. Patients taking bexarotene often need to take a drug to lower their cholesterol and triglyceride levels.

A new rexinoid called UAB30, just becoming available for laboratory studies, seems to have the potential to reduce even the high-lipid side effect.

"We will be testing this new compound, too, and if it turns out to be effective, these rexinoids will most likely become candidates for clinical trials in patients with precancerous nodules or bronchial dysplasia," You says. "If the trials show reduction of cancers, I think these drugs may well become routinely used for lung cancer prevention." Prevention is considered vital to decreasing the impact of lung cancer, which accounts for 32 percent of cancer deaths in men and 25 percent of cancer deaths in women. The majority of lung cancer patients are not diagnosed until their cancer has reached an advanced stage, and current treatment regimens do not substantially improve the outcome for most of these patients.

"Advanced or metastatic cancer is sort of a genius at adapting," You says. "By that point, the cancer cells that have survived ha
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Contact: Gwen Ericson
ericsong@wustl.edu
314-286-0141
Washington University School of Medicine
17-Jan-2006


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