Thursday, October 01, 2009
A friend of the bayblab sent me a link to a paper that just came out in Cancer Research showing promising results of Metformin against breast cancer. Not only does the drug seem to selectively kill CD44 positive breast cancer stem cells, but it seems to inhibit mammosphere formation. The puzzling part is that it seems to improve survival in nudes, but only when in combination with doxorubicin. Does this mean that killing the cancer stem cell is not sufficient to stop cancer growth? If this treatment works in humans, it might actually have a shot in combination with chemotherapy. In fact it's not the first time a link between metformin and cancer epidemiology in diabetic patients has been noticed. Hopefully the drug doesn't kill other "good" adult stem cells in the body since it is the most prescribed drug in the US (40M!). The paper also doesn't address the mechanism, but it may have something to do with MAPK, AMPK or PKC (then again what doesn't)...
Here is the abstract:
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]