Diabetes Drugs and Breast Cancer – What is the connection?

This week I wrote a post on diabetes and breast cancer (September 16th 2009), where I mentioned that the diabetes drug metformin, also known as Glucopahge or Fortamet has been shown to block tumor growth and prolong remission in mice.

I thought I’d write a bit more about this research, it interests me for two reasons:

1. I did my PhD in a diabetes research lab, looking for ways to turn the insulin gene off.
2. I spent two years working on a project studying the growth of breast cancer cells.

How on earth are these things connected? Why would a diabetes researcher work on cancer? When it comes down to basic research, it actually doesn’t matter what cell type you are working on, as long as you know how to do experiments on cells. I could study any disease you care to mention, cancer (of any type), HIV, arthritis, motor neuron disease, using the same laboratory experiments. The hard part is gaining enough knowledge to do experiments that matter and you can only do that by reading the scientific literature and discussing your work with other scientists. Every time you start a new research project you are on a steep, steep learning curve.

So, back to the paper, it is called “Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission” and was carried out in Kevin Strhul’s lab at Harvard Medical School, in the States.

The experiments were done on 4 different types of breast cells growing in plastic dishes in the lab (this is called “tissue culture” or “cell culture”). The four different breast cells are called:

These cells will be familiar to anyone working in breast cancer research, I have worked on MCF10A’s and MCF7′s and have read about the others in research papers.

Why did they use 4 different types of cell?

There are many different types of breast cancer and they respond differently to different treatments.  For instance the MCF7 cells have the estorgen receptor (that means they are ER positive), whereas the MDA-MB-468 cells lack the estorgen receptor (which means they are ER negative).

What did they do?

The researchers grew these cells in a dish, some cells they left untreated (a control), other cells they treated with the chemotherapy drug doxorubicin, the diabetes drug metformin, or both drugs (metformin and doxorubicin) at the same time.

The researchers believe that a breast cancer contains cancer cells and cancer stem cells. We need more research to prove if this is true, but they say that normal chemotherapy kills the cancer cells but cancer comes back because the stem cells are still alive.  In this paper they show that doxorubicin kills cancer cells (which we know) and that metformin kills the cancer stem cells.

They then went on to test this idea in mice and showed that mice treated with doxorubicin alone had a relapse after 20 days (the tumour started to grow again) where as mice treated with doxorubicin and metformin were in remission for 60 days. I know 60 days doesn’t sound like long, but remember mice only live for about 2 years, so actually that is a big improvement.

If you prefer to think in pictures rather than words, then the experiment is summarised below:

So what does this mean if you have diabetes?

You should be aware that diabetes may slightly increase your risk of breast cancer, if you notice anything unusual about your breasts, including any lumps your should tell your GP (even if it is embarrassing). It is possible that some of your diabetes medicines may lower your risk of cancer, so it is another reason you should aim to have good control of your disease.

What does this mean if you have breast cancer?

The study out today was done in mice and cells in a lab dish, there are now plans by the Canadian Institute of Health to carry out a clinical trial in humans. This study is just experimental and doesn’t change the standard treatments for breast cancer. However, if the trials in humans are successful it is likely that the treatment will be available more quickly than most new drugs, because metformin has already been approved for use (and shown to be safe) in humans.

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Hirsch, H., Iliopoulos, D., Tsichlis, P., & Struhl, K. (2009). Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission Cancer Research DOI: 10.1158/0008-5472.CAN-09-2994