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Reducing side effects of retinoic acid cancer treatment

ITHACA, N.Y. -- For some time doctors have been using a vitamin A derivative, retinoic acid (RA), to treat several cancers, particularly prostate cancer and leukemia, and they are now experimenting with the drug to treat breast cancer. The great drawback to RA, however, is that it requires high levels of the medication in order to turn genes "on" and "off," often triggering devastating and potentially fatal side effects.

Now, a Cornell University biochemist has learned how to make tumor cells up to 1,000 times more sensitive to RA so that much smaller doses would be required to flick the "on" and "off" switch (a process known as the induction of gene expression).

"This novel strategy for regulating the anticarcinogenic activity of retinoic acid has potential not only for treating tumors but also, perhaps, for protecting high-risk patients preventively," says Noa Noy, a professor of nutritional sciences at Cornell. "We have discovered that a naturally occurring protein in the cell can dramatically enhance the ability of RA to inhibit the proliferation of breast cancer cells, so that much less RA -- perhaps even the amount naturally present in the body -- is required to suppress tumor development."

The new findings are described in two recent articles in Molecular and Cellular Biology (April and July 2002).

RA belongs to a class of compounds known as retinoids that play key roles in regulating gene transcription and, therefore, govern multiple functions in the body, such as cell division and differentiation, immune response and embryonic development. They also control the development and spread of cancer cells, and some, including RA, can inhibit tumor growth by preventing cancer cell proliferation. Retinoids are now in clinical trials for treatment of head, neck and breast cancers, as well as for diabetes, arteriosclerosis and emphysema.

In the body, RA activates a protein in cells known as retinoic acid receptor (RAR) that binds
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Contact: Susan S. Lang
SSL4@cornell.edu
607-255-3613
Cornell University News Service
13-Aug-2002


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