New Hope for Aggressive Breast Cancer: Diabetes Drug Creates Treatment “Sweet Spot”

New research funded by Breast Cancer Now has shown that a drug commonly used to treat Type 2 diabetes could make breast cancer cells susceptible to new treatments.

Researchers used diabetes drug metformin to treat breast cancer stem cells, which are thought to be involved in the spread of breast cancer around the body. In experiments done in the lab, low-dose metformin treatment led to a shift in the way these cells make energy, opening up new ways to target aggressive forms of the disease.

In the future, this could lead to the development of new breast cancer drugs and treatment combinations which can target breast cancer stem cells.

Exploiting energy production in breast cancer stem cells

The new study, led by Dr Jeremy Blaydes from the University of Southampton, found that the diabetes drug metformin made triple negative breast cancer stem cells more reliant on glucose to make their energy and forced them to increase a process called glycolysis. Typically, breast cancer stem cells rely more on oxygen for energy production but metformin treatment changed this, creating new ways to stop the growth of these cells.

Following the shift in how these cells make their energy, the team found that the cells had also increased the activity of proteins known to drive the growth of breast cancer, called ‘CtBPs’. However, the researchers showed that turning off the CtBP genes, resulted in a 76% decrease in the growth of breast cancer stem cells. Molecules which block these proteins are currently being developed with the hope they could stop the growth of these cells in patients.

Dr Blaydes said: "Our work has given us the first glimpse into how changes in metabolism can alter the behaviour of breast cancer stem cells and reveal new targets for therapy. We are only beginning to scratch the surface in this area of research, and we now need to push forward the development of CtBP inhibitors as breast cancer drugs."

The researchers also noticed a change in the production of several other proteins. These could, in the future, be used as a measure to see if cancer stem cells have undergone this energy shift, indicating their vulnerability to CtBP blockers. This could lead to a much-needed new treatment option for patients with triple negative breast cancer.

Addressing a major unmet need in breast cancer

Over 8,000 women in the UK are diagnosed with triple negative breast cancer each year. Triple negative tends to be more aggressive than other types of breast cancer, and currently lacks targeted treatments available for other forms of the disease. Research is happening to develop new treatments for people living with this form of the disease to give them the best possible chance of survival.

Baroness Delyth Morgan, Chief Executive at Breast Cancer Care and Breast Cancer Now, said: "It’s really exciting that a diabetes drug could force breast cancer stem cells to change their energy supply to help us treat aggressive ‘triple negative’ tumours in the future."

With patients still lacking targeted therapies, and these tumours being more common in younger women, triple negative breast cancer remains one of the greatest areas of unmet need in breast cancer.

Why target breast cancer stem cells? 

Baroness Delyth Morgan said: "Breast cancer stem cells are thought to be central to the disease spreading around the body, where it becomes incurable, and so it’s incredibly promising that these early findings could lead to a new way to outsmart these elusive cells."

It’s also thought that breast cancer stem cells are involved in cancer becoming resistant to treatments. Finding new ways to target and kill breast cancer stem cells could stop cancers developing resistance to treatments and could prevent the disease from spreading to other parts of the body, giving everyone the best possible chance of survival.

What’s next?

The team now plan to develop and refine molecules which target CtBPs in breast cancer stem cells. It is hoped that targeting how these cells produce their energy could, in the future, create new treatment options for people living with breast cancer.

Researchers hope that they would be able to identify breast cancer stem cells which have undergone the change in the way they produce energy, allowing them to identify the patients that would benefit most from CtBP inhibitors.

Baroness Delyth Morgan added: "We look forward to further studies to develop and trial combinations of metformin and CtBP inhibitors in patients. By creating a new treatment ‘sweet spot’ in aggressive tumours, we hope this research could take us closer to our goal that by 2050, everyone who develops breast cancer will live, and live well."

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