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Diabetes drug metformin could suppress cancer cell activity

Type 2 diabetics who take metformin probably aren't expecting good news about their health. They're trying to manage elevated blood glucose levels, which put them at greater risk for most diseases associated with aging, especially heart disease, dementia and cancer. Well, maybe not cancer. Although diabetics face a higher risk of several types of cancer, new evidence suggests that metformin may actually suppress the activity of cancer cells, especially those most likely to make cancer spread.

Scientists have long observed that diabetes patients taking metformin (brand names such as Glucophage and Fortamet) are less likely to get cancer, and when they do, they have better outcomes. A study published last year in the Journal of Clinical Oncology found that 68 diabetic patients on metformin who had surgery and chemotherapy for breast cancer were three times more likely to remain cancer-free than the 87 diabetic patients not taking the drug. Even nondiabetic breast cancer patients included in the study didn't do as well.

A presentation at the American Association for Cancer Research in April reported that metformin appears to prevent lung cancer in smokers. A month earlier, McGill University researchers told the American Society of Clinical Oncology that the drug appears to inhibit the growth of prostate cancer cells — in the laboratory, at least. Japanese researchers just reported in Cancer Prevention Research that patients on metformin were less likely to experience a recurrence of precancerous polyps in their colon, while another study in the same issue reported that metformin reduced the incidence of lung cancer in mice by up to 53 percent.

What scientists haven't been able to figure out until now is why. Metformin lowers glucose in the blood. It also lowers levels of insulin needed to usher glucose into cells. Either reduction could have an anticancer effect. So could the drug itself.

Kevin Struhl of Harvard Medical School thinks the answer lies in metformin's ability to suppress cancer stem cells that fuel new tumors throughout the body.

"A cancer stem cell is a very aggressive tumor-forming cell that's resistant to chemotherapy," said Struhl, a professor of biological chemistry and molecular pharmacology. "Metformin selectively kills stem cells."

The stem cell hypothesis maintains that there are two types of cells in a tumor. The vast majority are cancer cells that are readily killed by chemotherapy. Stem cells make up only a small percentage of the tumor, but are more likely to survive chemotherapy and cause the cancer to recur.

Struhl thinks combining chemotherapy with metformin would lower the rate of recurrence. He holds a patent on a combination of metformin and low-dose chemotherapy, and has demonstrated its effectiveness on breast cancer in mice. A human study is getting under way in Canada to investigate whether metformin can prevent breast cancer recurrence. Struhl hopes to begin a study soon on human cancer survivors.

Metformin may even confer protection on people who have had cancer surgery, but who did not receive followup chemotherapy. "I think there's a rationale for that," Struhl said, "but it's very difficult to do the type of trial needed to show that, because you're talking about long-term use."

Another researcher attributes metformin's anticancer qualities to its ability to lower levels of insulin in the body.

"Cancer cells need glucose, but even the normal amount of glucose in the blood is enough to make cancer cells grow," said physician Michael Pollak of McGill University in Montreal. "If you give them extra glucose, it doesn't stimulate them, so the idea that high blood sugar stimulates cancer — that doesn't seem to be the case. However, some tumors love high insulin levels. Some colon, prostate and breast cancers need insulin."

Insulin makes cells grow, said Pollak, by helping glucose, their energy source, get through the cell membrane.

"But insulin does more than help cells take up nutrients," Pollak said. "Insulin also tells them to grow, multiply, divide. Some cancers see insulin as a growth signal."

In a recent paper in Diabetes Care, Pollak and his colleagues pointed out that metformin inhibits cancer cell proliferation, reduces the size of colonies of cancer cells, and causes a partial arrest of cancer cell lines. He suspects this is due to metformin's capacity to inhibit the ability of cancer cells to synthesize proteins.

So will metformin ever be given to healthy people to lower their cancer risk?

"It's too early to tell people concerned about cancer to take metformin," Pollak said, "but clinical trials are starting to address that question. Metformin can help lab mice, there's no question about that, but we do not have evidence yet for humans from clinical trials. The enthusiasm for finding answers is pretty high though."

Tom Valeo writes frequently about health matters. He can be reached at tom.valeo@gmail.com.

Diabetes drug metformin could suppress cancer cell activity 09/21/10 [Last modified: Tuesday, September 21, 2010 8:44am]

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