Metformin and Cancer (Continued)


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The Many Effects of Metformin

As a blood glucose-lowering medicine, metformin is known to have a number of effects on the body. The drug primarily works on the liver, acting to inhibit a process called gluconeogenesis, which is partly responsible for the body's natural production of glucose (gluconeogenesis is poorly regulated in people with type 2 diabetes, contributing to high blood glucose levels). Research also suggests metformin increases insulin sensitivity (the body's ability to respond to insulin), enhances glucose uptake in muscle tissue, and decreases the absorption of glucose from meals during digestion. Just how metformin drives these effects, however, is still unclear. It is believed that the drug works to increase the activity of AMP-activated protein kinase (AMPK), a widely prevalent protein involved in numerous processes in the body, including the response to insulin and the breakdown of glucose.

Researchers think AMPK's role in another process could be responsible for metformin's potential cancer-combating effects. Cancer cells are marked by their uncontrolled growth; due to alterations in their genetic makeup, cancerous cells begin to rapidly reproduce, leading to large masses of cells, or tumors. As AMPK is known to play a role in the coordination of cell reproduction, researchers propose that metformin could be acting to halt cancer's uncontrolled cell growth – sure enough, early laboratory research in isolated cancer cells indicated metformin could repress the cells' cancerous reproduction. Still, it is uncertain if the observed benefits can specifically be pinned down to metformin's effects on AMPK, leading to further hypotheses.

The latest research suggests metformin may actually selectively attack cancer stem cells, cells that make up a smaller portion of a tumor's mass but are particularly resistant to conventional chemotherapy. As chemotherapy is often unable to eliminate these cancer stem cells, they are able to re-grow post-treatment, leading to additional tumors – this is commonly referred to as "tumor relapse." In a recent study conducted by Dr. Kevin Struhl (Harvard Medical School), mice with breast cancer treated with both metformin and doxorubicin, a conventional chemotherapy, were free of tumors for at least two months following treatment. In contrast, mice treated with doxorubicin alone began to show signs of tumor re-growth in the same period, indicating the potential for use of metformin in combination with standard cancer treatments. This would be exciting, indeed, if this research were reproduced in humans.

Looking Ahead
A number of randomized clinical trials examining the use of metformin as a potential addition to standard chemotherapy are underway. A currently recruiting trial at Mount Sinai Hospital in Toronto is investigating whether taking metformin prior to surgical removal of breast tumors reduces the rate of tumor growth; another similarly scaled trial being conducted by the University Health Network in Toronto is examining the effects of metformin in patients with prostate cancer.

Overall, it is still too early to say what metformin's future will be as a cancer treatment. Similarly, the potential protective effect of metformin use in people with type 2 diabetes has yet to be conclusively shown in clinical trials; the associative evidence provided by retrospective studies does not prove that metformin is the cause of the observed reduction in cancer risk. However, as Dr. Pamela Goodwin, principal investigator of the aforementioned clinical trials, recently noted in the Journal of Clinical Oncology, "…the novelty of the intervention is high, and the potential for benefit is large." We will certainly be watching closely to see whether metformin will ultimately be prescribed in cancer treatment - stay tuned to diaTribe.

Eric Chang works at diaTribe, an independent, advertising-free e-newsletter for everyone eager to learn about the latest advances in diabetes management. diaTribe is your inside track on diabetes research and products – sign up here for your complimentary lifetime subscription!



NOTE: The information is not intended to be a replacement or substitute for consultation with a qualified medical professional or for professional medical advice related to diabetes or another medical condition. Please contact your physician or medical professional with any questions and concerns about your medical condition.



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Last Modified Date: November 08, 2013

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