Is your oncologist giving you Metformin with your chemotherapy?

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 cancercells within a tumor, cancer stem cells resist chemotherapeuticdrugs and can regenerate the various cell types in the tumor, thereby causing relapse of the disease. Thus, drugs that selectivelytarget cancer stem cells offer great promise for cancer treatment,particularly in combination with chemotherapy. Here, we showthat low doses of metformin, a standard drug for diabetes, inhibitscellular transformation and selectively kills cancer stem cellsin four genetically different types of breast cancer. The combinationof metformin and a well-defined chemotherapeutic agent, doxorubicin,kills both cancer stem cells and non-stem cancer cellsin culture. Furthermore, this combinatorial therapy reducestumor mass and prevents relapse much more effectively than eitherdrug alone in a xenograft mouse model. Mice seem to remain tumor-freefor at least 2 months after combinatorial therapy with metforminand doxorubicin is ended. These results provide further evidencesupporting the cancer stem cell hypothesis, and they providea rationale and experimental basis for using the combinationof metformin and chemotherapeutic drugs to improve treatmentof patients with breast (and possibly other) cancers. [CancerRes 2009;69(19):7507-11]