Dr. Weeks’ Comment: Here is another cheap adjunctive therapy your oncologist should know about. If this is news to your doctor, tell him or her to read the following:
Cancer Research 69, 7507, October 1, 2009. Published Online First September 14, 2009;
doi: 10.1158/0008-5472.CAN-09-2994
© 2009 American Association for Cancer Research
Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission
Heather A. Hirsch1, Dimitrios Iliopoulos1, Philip N. Tsichlis2 and Kevin Struhl1
1 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and 2 Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts
Requests for reprints: Kevin Struhl, Harvard University, 240 Longwood Avenue, Boston, MA 02115. Phone: 617-432-2104; Fax: 617-432-2529; E-mail: kevin@hms.harvard.edu
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. [Cancer Res 2009;69(19):7507-11]