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Process triggered by some cancer drugs causes tumors

A process used by some drugs to kill cancer cells in some body tissues may actually cause tumors when used in other tissue, scientists from MIT and the Whitehead Institute said in two studies released in the April 17 issue of Science.

The findings are important, researchers say, because some anti-cancer drugs in clinical trials are designed to kill diseased cells by triggering hypomethylation, which lowers the level of methylation. Methylation renders a gene active or inactive by affecting how the DNA is packaged into proteins without changing gene sequences.

Previous studies by the scientists have shown that drug-induced hypomethylation can protect against tumors arising in the intestinal tract (colon cancer). But in this new work, the scientists found that hypomethylation may cause tumors in the thymus of mice, suggesting that such drugs may do harm as well as good, said Professor Rudolf Jaenisch of biology, leader of the team that published these new studies.

"You have to know how you interfere with these cancer mechanisms," said Jaenisch. "At the moment we have two totally opposite results when we look in two different tissues. In the intestines, hypomethylation protects against cancer, and in the thymus it enhances cancer.

"It is very important to assess whether findings made in animal models apply to patients," he added.

Jaenisch's lab plans to extend this work by looking at other tumors, such as those of the pancreas, breast and liver.

For a longer version of this story, go to http://www.wi.mit.edu/nap/features/nap_feature_hypomethylatio.html.

A version of this article appeared in MIT Tech Talk on May 14, 2003.

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