In 2003, your support led pioneering researcher Professor Dario Alessi down an unexpected path to studying cancer risk in people with type 2 diabetes. A study concluded that if you have type 2 diabetes and you are treated with the drug metformin, you are less likely to develop cancer. Metformin is now being tested in over 100 clinical trials for the treatment and prevention of cancer.
Looking back at the project from Worldwide Cancer Research, it really was a small investment, £100,000 or so, but it has led to a whole area of work that had never been explored. You really can’t underestimate the knock on effect of these things.
Type 2 diabetes is a disease that causes an inability to regulate blood sugar levels, which can lead to too much sugar accumulating in the blood. Metformin can correct this error to some degree by helping cells in the body mop up the excess glucose and restoring normal blood sugar levels.
One way metformin works is by getting inside cells and hitting a molecular switch that turns the cells into little sponges, soaking up molecules of the sugar glucose floating in the blood.
This molecular switch is an enzyme called AMPK, a master controller of shuttling glucose molecules from the blood, into cells. When you exercise, AMPK in your muscle cells switches on and glucose is pulled into the cells where it is used as fuel.
Thanks to work by researchers like Professor Alessi, we now know that AMPK also plays an important role in cancer. In many cancers, the cells have lost their ability to use AMPK as a master switch.
This disruption to how the cells utilise energy contributes to their uncontrolled growth and proliferation – the underlying feature of all cancers.
Around the world there are over 120 clinical trials that are currently ongoing to test metformin as a treatment or preventive for cancer. There are also over 100 completed clinical trials, many with their results published. We talk to Professor Alessi about taking risks, Eureka moments, and ripple effects.
When we started our project in 2001, it was just a hunch. The project was a bit of a risk. We knew AMPK was activated by exercise putting stress on cells but we hadn’t worked out how AMPK was activated in cells, nor did we know anything about its role in cancer.
Through our project we discovered that a gene in our cells called LKB1, a known tumour suppressing gene, was able to activate AMPK. We did an experiment and saw this massive activation of the enzyme.
And we just knew that was it. The role of AMPK in cancer had not really been appreciated up to that point.
This was a big step forward for cancer research but it took an even bigger leap in thinking to realise the potential for how this finding could positively affect the lives of people with cancer.
It was definitely a Eureka moment. And then you start to realise the implications of the results. It didn’t take long, weeks maybe, to make the connection.
You start thinking, how is this all linked? You have an enzyme that’s involved with exercise and diabetes, and a gene that when mutated causes malignant tumours potentially by stopping the enzyme from working. And then you remember that the drug metformin can switch on this enzyme, so maybe metformin could also be a way to counteract the development of tumours.
Professor Alessi reasoned that since metformin was able to switch on AMPK to help people with diabetes, maybe it could also provide protection against cancer. To test this, he dove into the clinical records of nearly 12,000 people diagnosed and treated for type 2 diabetes, and looked at how many of them went on to develop cancer during their lifetime.
Analysis of the data revealed people with type 2 diabetes who were treated with metformin were at a lower risk of developing cancer.
Around 2 per cent of the world’s population take metformin for diabetes. And there’s a great quote from Professor Lewis Cantley at Cornell University, who said: ‘Metformin may have already saved more people from cancer deaths than any other drug in history’. But we just won’t know it yet.
The results from our project stimulated huge amounts of subsequent work. There must be thousands of research papers published and hundreds of clinical trials involving metformin and cancer. The impact of this work has really opened the door to studies that will lead to new therapies for many different diseases, including cancer.
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