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- Cancer Res. 2009 Oct 1;69(19):7507-11. Epub 2009 Sep 14.
selectively targets cancer stem cells, and acts together with
chemotherapy to block tumor growth and prolong remission.
Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K.
of Biological Chemistry and Molecular Pharmacology, Harvard Medical
School and Molecular Oncology Research Institute, Tufts Medical Center,
Boston, MA 02115, USA.
The cancer stem cell
hypothesis suggests that, unlike most cancer cells within a tumor,
cancer stem cells resist chemotherapeutic drugs and can regenerate the
various cell types in the tumor, thereby causing relapse of the
disease. Thus, drugs that selectively target cancer stem cells offer
great promise for cancer treatment, particularly in combination with
chemotherapy. Here, we show that low doses of metformin, a standard
drug for diabetes, inhibits cellular transformation and selectively
kills cancer stem cells in four genetically different types of breast
cancer. The combination of metformin and a well-defined
chemotherapeutic agent, doxorubicin, kills both cancer stem cells and
non-stem cancer cells in culture. Furthermore, this combinatorial
therapy reduces tumor mass and prevents relapse much more effectively
than either drug alone in a xenograft mouse model. Mice seem to remain
tumor-free for at least 2 months after combinatorial therapy with
metformin and doxorubicin is ended. These results provide further
evidence supporting the cancer stem cell hypothesis, and they provide a
rationale and experimental basis for using the combination of metformin
and chemotherapeutic drugs to improve treatment of patients with breast
(and possibly other) cancers.