Diabetes drug kills cancer stem cells in combination treatment in mice
In a one-two punch, a familiar diabetes drug reduced tumors faster and prolonged remission in mice longer than chemotherapy alone by targeting cancer stem cells, Harvard Medical School researchers reported in Cancer Research, a journal of the American Association for Cancer Research.
"We have found a compound selective for cancer stem cells," said lead researcher Kevin Struhl, Ph.D., the David Wesley Gaiser professor of biological chemistry and molecular pharmacology at Harvard Medical School. "What's different is that ours is a first-line diabetes drug."
These findings add to a growing body of preliminary evidence in cells, mice and people that metformin may improve breast cancer outcomes in people. In this study, the diabetes drug seemed to work independently of its ability to improve insulin sensitivity and lower blood sugar and insulin levels, all of which are also associated with better breast cancer outcomes.
The results fit within the cancer stem cell hypothesis, an intensely studied idea that small subsets of cancer cells have a special power to initiate tumors, fuel tumor growth and promote recurrence of cancer. Cancer stem cells appear to resist conventional chemotherapies, which kill the bulk of the tumor.
"There is a big desire to find drugs specific to cancer stem cells," said Struhl. "The cancer stem cell hypothesis says you cannot cure cancer unless you also get rid of the cancer stem cells. From a purely practical point of view, this could be tested in humans. It's already [in use as] a first-line diabetes drug."
The possible usefulness of a diabetes drug against cancer lends credence to an emerging idea that, in the vast and complex alphabet soup of molecular interactions within cells, a relatively few biological pathways will turn out to be most important for many different diseases, Struhl suggested.
In experiments led by postdoctoral fellows Heather Hirsch, Ph.D., and Dimitrios Iliopoulos, Ph.D., the combination of metformin and the cancer drug doxorubicin killed human cancer stem cells and non-stem cancer cells in culture. The researchers used four genetically distinct breast cancer cell lines.
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