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Discovery blocks cancer drug's toxic side effect
Date:11/4/2010

A debilitating side effect of a widely used but harshly potent treatment for colon cancer could be eliminated if a promising new laboratory discovery bears fruit.

The pre-clinical finding, published in the Nov. 5, 2010, issue of the journal Science, relates to the drug CPT-11, or Irinotecan, a chemotherapeutic agent used against colon cancer and other solid malignancies. It is believed to be the first successful targeting of an enzyme in symbiotic bacteria found in the digestive system.

While it has proven a valuable tool for attacking tumors, CPT-11 can also cause severe diarrhea, which limits the dosage that patients can tolerate, curbing the drugs potential effectiveness.

Now, a team of researchers led by Matthew R. Redinbo, Ph.D., from the University of North Carolina at Chapel Hill, has discovered it is possible to target and block the enzyme, beta glucuronidase, which was thought to play a major role in the gastric side effects.

First, the scientists had to overcome a major hurdle: the culprit enzymes are found in microbes in the gut that play a major role in human health, so eliminating the anticancer drugs toxicity without making things worse for patients was a real challenge, Redinbo said.

We need to retain our intestinal bacteria they help us digest food, make critical vitamins and protect us from infection, said Redinbo, professor and chair of the chemistry department in the UNC College of Arts and Sciences and a member of the UNC Lineberger Comprehensive Cancer Center. This targeted approach stops the one bacterial protein thought to cause the drugs devastating side effect, but without damaging the beneficial microbes or the intestines.

The trouble with CPT-11 begins part way through the bodys process of excreting the drug, presumably after it has already killed tumor cells and been rendered inert. When it reaches the intestines, beta glucuronidase enzymes in the gut bacteria snip a
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Contact: Dianne Shaw
dgs@med.unc.edu
919-966-5905
University of North Carolina School of Medicine
Source:Eurekalert

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