Diabetes Drug Fights Breast Cancer

Metformin Kills Breast Cancer Stem Cells, May Fight Many Cancers

From the WebMD Archives

Sept. 14, 2009 - The next breakthrough breast cancer treatment may be a diabetes drug already on the shelves of nearly every pharmacy.

The drug is metformin, available generically and under brand names such as Glucophage and Fortamet. A growing body of evidence suggests that diabetes patients taking metformin are less likely to get cancer, and have better outcomes if they do get cancer, than those not taking the drug.

Now Harvard researcher Kevin Struhl, PhD, and colleagues find that metformin can kill breast cancer stem cells, thought to be the cells responsible for breast cancer spread and recurrence.

And in mice carrying human breast cancers, metformin made standard chemotherapy vastly more effective. Mice treated with the combination remain cancer-free for four months, unlike mice treated with either drug alone.

"We have discovered new properties of metformin that can be of some use in cancer treatment and even prevention," Struhl said at a news conference held to announce the findings.

While his current study looked at metformin's effects on breast cancer, Struhl says the drug may affect other types of cancer as well.

"Although our studies were pretty much done on breast cancer cells, a lot of the principles are not specific just to breast cancer," Struhl said. "A lot of data shows lower cancer risk -- not just breast cancer -- in people taking metformin for diabetes."

Metformin Kills Cancer Stem Cells

What's so special about yet another drug that kills cancer cells in mice?

For one thing, the kind of cancer cells metformin targets are cancer stem cells, which are resistant to standard chemotherapy.

"This is the first time it's been shown that metformin may have an effect on these very resistant cancer cells. It is very exciting research," Dana-Farber Cancer Institute researcher Jennifer A Ligibel, MD, said at the news conference.

The very existence of cancer stem cells has been debated. That debate is now "water under the bridge," Frank Rauscher, PhD, suggested at the news conference. Rauscher, a cancer researcher at the Wistar Institute, is editor-in-chief of Cancer Research, which published the Struhl study in today's advance online edition.

Continued

Struhl says cancer stem cells are "far more nasty" than regular cancer cells.

"The bulk of the cells in a tumor are cancer cells which grow but are killed by chemotherapy," Struhl says. "But there is also a small population of cancer stem cells, which are better able to form tumors on their own and more resistant to chemotherapy than cancer cells. After standard chemotherapy, they can remain and essentially regenerate the tumor, and the disease is back again."

Different researchers have recently described new compounds that selectively kill cancer stem cells. Whether these compounds might one day become safe and effective cancer drugs remains to be shown.

Struhl -- who, with Harvard Medical School, holds a patent on the combined use of metformin and low-dose chemotherapy -- says metformin is already known to be safe and merely needs to be proven effective in human clinical trials.

Easier Cancer Chemo With Metformin?

Another reason researchers are excited about the study findings is that metformin and standard chemotherapy seem to make each other work better.

"Because of this synergy with chemotherapy, metformin could be used with lower doses of chemotherapy," Struhl suggests. "Chemotherapy is quite a toxic thing for people to deal with, and if one could lower the dose that would be very nice."

Metformin itself has an outstanding safety record.

"This drug at low doses can be considered a very good candidate for cancer prevention before a person has any cancer at all," Rauscher said. "The hope is we can use a drug like metformin and continue to deplete the levels of these inherently chemotherapy-resistant, dormant cancer stem cells."

Can Metformin Prevent Breast Cancer Recurrence?

Ligibel, who was not involved in the Struhl study, has argued that metformin should be tested in people.

Taking her own advice, she is participating in a human study led by Canada's national cancer institute that will test whether metformin can prevent breast cancer from coming back after treatment. The study, which will take place at multiple cancer centers in Canada and the U.S., has not yet begun enrollment.

Unfortunately, Ligibel said, there are no plans for studies combining metformin with chemotherapy. But Struhl said that because metformin is an approved drug, such studies could begin relatively soon.

"We are hoping for researchers to actually try that experiment," Struhl said. "The idea of using this as a combined treatment is the main point of our paper."

"These concepts should be moved forward in clinical trials," Rauscher agreed.

WebMD Health News Reviewed by Louise Chang, MD on September 14, 2009

Sources

SOURCES:

Hirsch, H.A. Cancer Research, Oct. 1, 2009; vol 69, published online ahead of print Sept. 14, 2009.

Goodwin, P.J. and Ligibel, J.A. Journal of Clinical Oncology, July 10, 2009; vol 27: pp 3271-3273.

Kevin Struhl, PhD, professor of biological chemistry and molecular pharmacology, Harvard Medical School, Boston

Frank Rauscher, III, PhD, editor in chief, Cancer Research; professor of gene expression and regulation, The Wistar Institute, Philadelphia

Jennifer Ligibel, MD, medical oncologist, Dana-Farber Cancer Institute; instructor in medicine, Harvard Medical School, Boston.

News release, Harvard Medical School.

News release, American Association for Cancer Research.

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