Metformin Kills Breast Cancer Stem Cells in Mice

GlucophageA common diabetes drug might be able to reduce tumors faster and prolong remission in mice longer than chemotherapy alone by targeting cancer stem cells, according to Harvard researchers.

These findings suggest that metformin drug (Glucophage, Bristol-Myers Squibb) might be able to improve breast cancer outcomes in humans. In this study, the drug seemed to work independently of its ability to improve insulin sensitivity and lower blood glucose and insulin levels, all of which are also associated with better breast cancer outcomes.

The results fit within the idea that small subsets of cancer cells have a special power to initiate tumors, fuel tumor growth, and promote the recurrence of cancer. Cancer stem cells appear to resist conventional chemotherapies, which kill the bulk of the tumor. The cancer stem cell hypothesis is that cancer cannot be cured unless the stems cells are also eliminated.

In experiments, generic metformin plus the cancer drug doxorubicin (Adriamycin) killed human cancer stem cells and non-stem cancer cells in culture. Four genetically distinct breast cancer cell lines were used.

In mice, pretreatment with metformin prevented the otherwise dramatic ability of human breast cancer stem cells to form tumors. In other mice, in which tumors took hold for 10 days, the combination therapy also reduced tumor mass more quickly and prevented relapse for a longer time compared with doxorubicin alone. In the two months between the end of treatment and the end of the experiment, tumors regrew in the mice treated with chemotherapy alone but not in those who received both drugs. Metformin was ineffective in treating tumors when used alone.

A large-scale phase 2 trial is planned to study generic metformin’s impact on recurrence in women treated for early-stage breast cancer. So far, observational studies have suggested a lower risk of cancers, including breast cancer, and better responses to chemotherapy in patients with diabetes who received metformin.

The researchers were encouraged by the low dose of metformin needed for the effect in the laboratory, compared with the amount needed in basic diabetes research.

Sources: Cancer Res, September 14, 2009; The Wall Street Journal, September
15, 2009