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Study Reveals How Common Painkillers Fight Cancer

NSAIDs like aspirin and ibuprofen boost a tumor-killing molecule

FRIDAY, Dec. 15, 2006 (HealthDay News) -- For years, experts have noted that people who take nonsteroidal anti-inflammatory drugs (NSAIDs) for pain relief also lower their risk for a variety of cancers.

Now, scientists believe they know why that happens.

New research shows that NSAIDs -- which include aspirin, ibuprofen, Aleve and Celebrex -- boost the level of a cellular molecule that causes malignant cells to die off.

The finding "opens up our understanding of how anti-inflammatory drugs are effective against cancer cells. This could also lead to new drug development and of monitoring drugs' effect on cancer cells," said study senior author Towia Libermann, director of the Genomics Center at Beth Israel Deaconess Medical Center in Boston.

His team published its findings in the Dec. 15 issue of Cancer Research.

The millions of Americans who regularly take a daily NSAID to ease arthritis or other pain have long gotten an added bonus in terms of reduced cancer risk. For example, a study released this spring found that women who took daily aspirin had lower odds of developing a particularly aggressive form of breast cancer. Trials have also been conducted that suggest that Celebrex might reduce risks for precancerous colorectal polyps.

There are other indicators linking chronic inflammation and cancer. "For example, people with inflammatory bowel disease have a significantly higher risk for colon cancer than the regular population," Libermann said, and there's also a highly aggressive breast malignancy -- called inflammatory breast cancer -- that is marked by tissue inflammation.

So, it makes sense that drugs that subdue inflammation might also beat back cancer. But how?

To answer that question, Libermann's team used high-tech gene microarray analyses to examine more than 20,000 genes they knew were activated in the presence of NSAIDs.

They discovered that one gene, in particular, was highly activated to produce a particular cytokine (a protein-signaling molecule) called MDA-7/IL-24.

As the level of this cytokine rose, the ability of cancer cells to avoid programmed cell death declined.

"We showed this in different types of cancer cells and with different types of anti-inflammatory drugs," said Libermann, who is also associate professor of medicine at Harvard Medical School. "In fact, drugs that were not active in killing cancer cells did not induce this cytokine, while drugs that were able to kill cancer cells did induce this cytokine."

Accoring to Libermann, the finding unravels the mystery of how NSAIDs fight malignancy.

Not everyone is convinced, however. Dr. Michael Thun, head of epidemiological research at the American Cancer Society, called the study "interesting" but noted that the work focused on tumor cells -- not the pre-malignant cells, such as those found in colon polyps, that have shown to be most inhibited by NSAIDs. "That's one issue that needs to be looked at further," he said.

Thun also noted that the doses used in Libermann's study far exceed those of everyday NSAID use in the general population.

Both scientists agreed that it is premature to recommend that people at higher risk for cancer take NSAIDs.

"All of the studies done so far were done only in cell cultures and animal models," Libermann stressed. "Nothing's been done in patients yet -- maybe patients would need 100 times more of the drug to get any real effect. And that would have such terrible side effects that it wouldn't work."

Thun agreed. "At this point, there is no health organization that recommends taking aspirin or related drugs to prevent any cancer," he said. The expert added that while aspirin's safety profile remains uncontroversial, "taking aspirin-like drugs [such as Celebrex or Aleve] for prevention has been pretty much ruled out because of heart risk."

But Libermann believes researchers will now start working on refining NSAIDs to provide maximum anti-cancer benefit with minimum risk. "We can take some of these anti-inflammatory drugs and make them more specific to inducing this cytokine in a very potent way -- without some of the side effects that anti-inflammatory drugs can have," he said.

Measuring blood levels of MDA-7/IL-24 might also allow doctors to someday "tailor treatment and monitor how effective a particular drug is," Libermann said. "Because every patient will respond differently."

More information

There's more on NSAIDs and colon cancer at the American Cancer Society.

SOURCES: Towia Libermann, Ph.D., director, Genomics Center, Beth Israel Deaconess Medical Center, and associate professor, medicine, Harvard Medical School, Boston; Michael Thun, M.D., head, epidemiological research, American Cancer Society; Dec. 15, 2006, Cancer Research
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