|| Thursday: August 31: 2023 || ά. A drug, being developed to combat metabolic diseases, such as, Type Two Diabetes and Alzheimer’s Disease may offer new treatment hope for people with chronic Myeloid Leukaemia:CML, a form of blood cancer. This 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 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 Two 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. The 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 this that TKIs do not target the important CML stem cells, that drive the disease.

Professor Vignir Helgason, the 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.”

Ms 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.” 

Mr Jerry Colca, Co-founder of Metabolic Solutions Development Company, which is developing the investigational drug MSDC-0160, said, ‘’We are excited about the potential of the mechanism of action of new insulin sensitisers, demonstrated in this Study.”

The Study: Pyruvate anaplerosis is a targetable vulnerability in persistent leukaemic stem cells:  Published in Nature Communications. This research 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. :::ω::: 

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