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A drug being developed to combat metabolic diseases such as type 2 diabetes and Alzheimer’s disease may offer new treatment hope for people with chronic myeloid leukaemia (CML), a form of blood cancer.

The new study, led by the University of Glasgow and published in Nature Communications, focused on understanding the unique role glucose plays in the behaviour of treatment-resistant CML cancer cells. Encouragingly, the research team found that targeting CML cells with an investigational diabetes drug prevented them from absorbing glucose, weakening them and potentially making them more susceptible to cancer treatments.

Previous research has shown that targeting how cancer cells use nutrients such as glucose to survive, may open the door to promising new treatment opportunities.

The researchers for this study found that CML stem cells – the vital cells that drive the disease – used glucose to fuel their mitochondria, the energy powerhouse of the cell. By doing that, these stem cells were also arming themselves to evade current treatments.

To combat this, researchers successfully targeted the CML stem cells using a drug that stops glucose getting into their mitochondria. The same drug has been tested in other clinical trials for the treatment of type 2 diabetes and Alzheimer’s disease. The research team is now exploring the possibility of moving findings into a clinical trial to see if combining this drug with current CML treatments would benefit patients.

At present, CML patients are treated with tyrosine kinase inhibitors, otherwise known as TKIs, which have transformed the clinical management of the disease. Treatment of patients with TKIs alone rarely cures the disease, but they can hold its advancement at bay. As a result, most patients need to remain on TKIs for the rest of their lives, with associated side effects and the risk of developing resistance to the drugs. The main reason a cure for CML is not yet possible is that TKIs do not target the important CML stem cells that drive the disease.

Professor Vignir Helgason, lead author of the study from the University of Glasgow, said: “Research has shown that cancer cells often rely on increased uptake of specific nutrients – sugar, proteins or fats – to survive. This suggests that if we can use drugs to target that nutrient uptake, it may in turn improve cancer treatments.

“Our study investigated specific nutrient “addictions” in CML cancer cells. We were able to reveal that CML cancer cells use an increased amount of glucose to support their nutritional needs. Encouragingly, we were also able to show that the same cancer cells were sensitive to a newly developed anti-diabetic drug that prevents a normal breakdown of glucose, blocking the cells’ ability to absorb it.”

Dr Kevin Rattigan, co-author of the study, from the University of Glasgow’s School of Cancer Sciences, said: “Our study has revealed that the addiction to glucose is an Achilles heel for the CML stem cells that are resistant to current therapies. We were also able to show that a newly developed drug can prevent CML stem cells using glucose for energy. This breakthrough may lead to improved therapy options and outcomes for patients.”

Sarah McDonald, Blood Cancer UK’s Deputy Director of Research said:
“Blood cancer is the UK’s third biggest cancer killer and receiving a blood cancer diagnosis can be life changing. While there is currently no cure for this form of blood cancer- chronic myeloid leukaemia (CML) - research findings like these give the 750 people diagnosed with CML each year in the UK hope. Looking at how existing drugs can be used in other conditions maximises their potential and provides insight into where future research can help those with CML. At Blood Cancer UK we are committed to bringing about new treatments for the blood cancer community who desperately deserve it.”

Jerry Colca, cofounder of Metabolic Solutions Development Company who are developing the investigational drug MSDC-0160 studied in this paper, said: “We are excited about the potential of the mechanism of action of new insulin sensitizers demonstrated in this study.”

The study, ‘Pyruvate anaplerosis is a targetable vulnerability in persistent leukaemic
stem cells’ is published in Nature Communications. This work was mainly funded by Blood Cancer UK and Cancer Research UK with additional support from The Howat Foundation, The Kay Kendall Leukemia Fund, Tenovus Scotland and Friends of Paul O’Gorman Leukaemia Research Centre.

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Enquiries: ali.howard@glasgow.ac.uk or elizabeth.mcmeekin@glasgow.ac.uk / 0141 330 6557 or 0141 330 4831

First published: 17 August 2023