Diabetes Drug Fights Breast Cancer

Metformin Kills Breast Cancer Stem Cells, May Fight Many Cancers

Medically Reviewed by Louise Chang, MD on September 14, 2009
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 inmice?

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

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

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

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

"The bulk of the cells in a tumor are cancer cells which grow but are killedby chemotherapy," Struhl says. "But there is also a small population of cancerstem cells, which are better able to form tumors on their own and moreresistant to chemotherapy than cancer cells. After standard chemotherapy, theycan remain and essentially regenerate the tumor, and the disease is backagain."

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

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

Easier Cancer Chemo With Metformin?

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

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

Metformin itself has an outstanding safety record.

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

Can Metformin Prevent Breast Cancer Recurrence?

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

Taking her own advice, she is participating in a human study led by Canada'snational cancer institute that will test whether metformin can prevent breastcancer from coming back after treatment. The study, which will take place atmultiple cancer centers in Canada and the U.S., has not yet begunenrollment.

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

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

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

Show 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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