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New pathway found to enhance cancer treatment

HANOVER, NH -- Dartmouth Medical School (DMS) research points to a potentially larger role for retinoids in the treatment of cancer. The removal of a cell protein called RIP140 has significantly enhanced the cancer treatment and prevention abilities of retinoids in a laboratory setting.

Retinoids, compounds derived from Vitamin A, work by turning on proteins called retinoid receptors, which increase the abundance of a panel of retinoid "target genes." The new study, in the November 7 issue of the Journal of Biological Chemistry, builds on the prior DMS discovery that a potential retinoid receptor inhibitory protein called RIP140 is a byproduct of one of these target genes.

Now the research team has found that RIP140 is responsible for repressing the retinoid receptors, adversely affecting the ability of retinoids to differentiate cancer cells and slow tumor growth in experiments using testicular cancer cells.

"Once RIP140 was removed, growth of cancer cells was repressed by retinoids at a faster rate compared to experiments where RIP140 was present," said Kristina White, who performed the experiments with Mark Yore, both graduate students in pharmacology and toxicology. "We also noticed that anticancer genes known to be turned on by retinoids were turned on to a much greater extent," said White.

Retinoids have been known to have anti-tumor properties in the clinical setting. Based on laboratory findings, retinoids have the potential to treat and prevent a variety of leukemia and solid cancers, primarily by causing cancers to "mature" or "differentiate" and thus more closely resemble normal cells. This strategy may have less severe side-affects compared to conventional chemotherapy and may be a particularly valuable strategy in preventing cancer in high-risk individuals. However, thus far retinoids have only proven to be useful toward a small subset of cancer types in people.

"We were surprised at how much better retinoi
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Contact: Andy Nordhoff
DMS.Communications@dartmouth.edu
603-650-1492
Dartmouth Medical School
5-Nov-2003


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