Teaching an old drug new tricks – using metformin to treat cancer
Metformin is commonly used to control blood sugar levels in people with type II diabetes. Current renewed interest in the drug all started back in 2003, when three research groups, including that of Worldwide Cancer Research-funded Professor Dario Alessi, published astonishing data suggesting it could be a potent new anticancer drug.
Can a diabetes drug really prevent cancer?
Professor Dario Alessi at the University of Dundee was one of the researchers whose pioneering work helped bring metformin back into focus.
Professor Alessi’s team was able to establish one of the first clear links showing cancer could in part be driven by faulty metabolic processes (how the cells use energy).
The team were able to prove that the (anticancer) tumour suppressor protein LKB1 activates a molecule called AMPK. Until then it had mainly been associated with cell energy use, not cancer. Importantly, metformin is known to target AMPK.
A (not so) crazy idea
Based on their findings with AMPK and LKB1 he approached Professor Andrew Morris, a prominent diabetes doctor, about checking his patient database.
Professor Alessi told us “At first he thought I was mad, I had to speak to him 3 or 4 times, before he agreed to do a retrospective analysis of his database. When he did, he randomly selected those who did or did not take metformin for diabetes.
As I had predicted, there was 20-25% fewer cancer diagnoses in those who took metformin and we published these findings in the British Medical Journal. Since then there have been around 30-40 papers from epidemiologists, who also confirm this 20-25% reduction suggesting metformin has a protective effect against the disease.”
This work helped kick off a whole new era of research investigating cancer metabolism. And metformin has been in the spotlight ever since.
What cancer types could metformin be used for?
There are currently over 200 clinical trials investigating metformin’s potential activity against many different types of cancer, including bowel cancer, prostate cancer, and melanoma skin cancer. In fact one of the melanoma trials is happening thanks to our funding.
Metformin was recently in the news as a potential treatment for the rare disease chronic myeloid leukaemia.
But metformin isn’t the only drug to have been repurposed.
Thalidomide, the anti-morning sickness drug renowned for causing serious birth defects in children, is used to treat the blood cancer myeloma.
And recently, with Worldwide Cancer Research funding, scientists discovered that cheap drugs used to treat parasitic worms and conditions such as river blindness could beat a type of breast cancer that often fails to respond to standard therapies.
Back in 2006 Professor Richard Marais, formerly at the Institute of Cancer Research, found that metformin increased the growth of one type of malignant melanoma skin cancer, but stopped the growth of another type.
He discovered that the effects of metformin on melanoma cells depend on their genetic background. This finding is of vital clinical interest, as it suggests that patients with that genetic background should not be prescribed metformin.
A second grant from us, starting in 2009, allowed him to build on those findings, by studying how metformin is able to stop tumour growth. He found that it interacts with the VEGF signalling pathway. This pathway is involved in the development of new blood vessels, an essential part of tumour growth. Drugs that block the VEGF pathway are commonly used in cancer treatment.
He also found that the combination of metformin and anti-VEGF drugs was more efficient than the anti-VEGF drugs alone, and this treatment is currently being investigated in melanoma patients, in a phase II clinical trial.
Worldwide Cancer Research is proud to have supported both Professor Alessi’s and Professor Marais’ ground-breaking work.
Professor Alessi told us:
"When we started working on this, it was a completely new project. We had very little preliminary data, the committee showed a very big act of faith. Worldwide Cancer Research funding was absolutely critical, nothing would have happened in this area without this funding, no bit of funding I have received has ever achieved quite so much."
Metformin is no ‘miracle cure’, and it’s not without side-effects. Much work needs to be done to establish if, and how, metformin could potentially help patients at risk of cancer. But thanks to that early research carried out by Professor Alessi and others, today we are much closer to finding out.
Pictured: Professor Dario Alessi
Diabetes drug may help in leukaemia.
Thalidomide as a treatment for myeloma.
Anti-parasite drugs for river blindness could treat breast cancer.