A new drug in development for metabolic diseases could also benefit people with chronic myeloid leukaemia (CML).
Researchers found that targeting CML cells with MSDC-0160, a drug being tested for type 2 diabetes and Alzheimer’s disease, weakened the cells and could potentially make them more susceptible to cancer treatments. The study was led by the University of Glasgow and published in Nature Communications last week.
The team found CML stem cells used glucose to fuel their mitochondria and by doing so, the stem cells were able to evade current treatments.
To combat this, the CML stem cells were targeted using MSDC-0160, which prevents pyruvate (a molecule made from the breakdown of glucose) from getting into their mitochondria.
Lead study author Professor Vignir Helgason, 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, from the University of Glasgow’s School of Cancer Sciences, added: “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.”
Rattigan KM, Brabcova Z, Sarnello D, Zarou MM, Roy K, Kwan R, de Beauchamp L, Dawson A, Ianniciello A, Khalaf A, Kalkman ER, Scott MT, Dunn K, Sumpton D, Michie AM, Copland M, Tardito S, Gottlieb E, Vignir Helgason G. (2023) “Pyruvate anaplerosis is a targetable vulnerability in persistent leukaemic stem cells.” Nature Communications, doi: 10.1038/s41467-023-40222-z.
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