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Different drug combinations work best for prevention versus treatment of colorectal tumors
Date:4/7/2013

unnatural waythrough exposure to carcinogenic chemicalswhereas in humans, cancer often has genetic origins.

To evaluate the effectiveness of sulindac and atorvastatin in an animal model more relevant to humans, Chang, Clapper and their colleagues used a unique mouse that had genetic alterations that cause them to develop multiple colorectal adenomas, without exposure to carcinogens. "No one had previously tested the effectiveness of this drug combination against colorectal cancer originating from alterations in the genome," Clapper says. "In some ways, using this type of preclinical tumor model represents a new paradigm for doing prevention studies and therapeutic studies."

In the new study, the researchers treated the mice with either drug alone or in combination for 100 days and used colonoscopic examinations to evaluate the presence and size of tumors before and after treatment. In mice that had tumors prior to treatment, only combination therapy reduced the number of adenomas in the colon by the end of the treatment period.

The results were strikingly different in mice that were tumor-free when treatment began. In these mice, exposure to atorvastatin alone or in combination with sulindac resulted in about a three-fold increase in the percentage of mice that were tumor-free by the end of the treatment period. Among these mice, 44 percent of those treated with atorvastatin alone and 30 percent of those treated with both drugs did not develop tumors, compared with 13 percent of mice that received no treatment and nine percent that received sulindac alone. Moreover, atorvastatin treatment completely inhibited the formation of microscopic adenomas in these mice.

The findings demonstrate that the effectiveness of the two drugs at preventing and treating colorectal adenomas depends on whether tumors are present prior to the onset of treatment. "Based on this study, we're able to say that if you don't have a tumor to begin with, ma
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Contact: Diana Quattrone
diana.quattrone@fccc.edu
215-728-7784
Fox Chase Cancer Center
Source:Eurekalert

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