New Treatment For Chronic Myeloid Leukaemia: A drug under development to treat metabolic diseases such as type 2 diabetes and Alzheimer’s disease may offer new treatment hope for persons with chronic myeloid leukaemia (CML), a type of blood cancer.
The new study, led by the University of Glasgow and published in Nature Communications, sought to comprehend the unique function glucose plays in the behaviour of CML cancer cells that are resistant to treatment. Encouragingly, the research team discovered that targeting CML cells with an investigational diabetes drug prevented them from absorbing glucose, thereby diminishing them and making them potentially more susceptible to cancer treatments.
Targeting how cancer cells utilise nutrients such as glucose for survival may present intriguing new treatment opportunities, according to previous research.
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This study’s researchers discovered that CML stem cells, the disease-driving cells, used glucose to sustain their mitochondria, the cell’s energy factory. In doing so, these stem cells also armed themselves to resist current therapies.
To counteract this, scientists effectively targeted CML stem cells with a drug that prevents glucose from entering their mitochondria. In other clinical trials, the same drug has been used to treat type 2 diabetes and Alzheimer’s disease. The research team is currently investigating the possibility of conducting a clinical trial to determine whether combining this substance with existing CML treatments would be beneficial to patients.
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Patients with CML are currently treated with tyrosine kinase inhibitors, or TKIs, which have revolutionised the clinical management of the disease. Patients treated with TKIs alone are rarely cured of their disease, but they can halt its progression. As a consequence, the majority of patients must remain on TKIs for the remainder of their lives, with the associated side effects and risk of developing drug resistance. TKIs do not target the vital CML stem cells that drive the disease, which is the primary reason why a cure for CML is not yet feasible.
Professor Vignir Helgason, the study’s primary author from the University of Glasgow, stated, “Research has demonstrated that cancer cells frequently rely on increased uptake of specific nutrients – sugar, proteins, and fats – to survive. This suggests that if we can target nutrient absorption with medications, cancer treatments may be enhanced.
“Our investigation investigated the “addictions” of CML cancer cells to specific nutrients. We were able to determine that CML cancer cells require a greater quantity of glucose to meet their nutritional requirements. Encouragingly, we were also able to demonstrate that the same cancer cells were sensitive to a newly developed anti-diabetic drug that blocks the cells’ capacity to absorb glucose by preventing its normal breakdown.”
Research Analysis
Dr. Kevin Rattigan, co-author of the study from the University of Glasgow’s School of Cancer Sciences, stated, “Our research has revealed that the CML stem cells that are resistant to current therapies have a weakness in their addiction to glucose. In addition, we were able to demonstrate that a newly developed drug can prevent CML stem cells from utilising glucose as an energy source. This discovery may result in enhanced treatment options and patient outcomes.”
Sarah McDonald, Deputy Director of Research at Blood Cancer UK, stated, “Blood cancer is the third leading cause of cancer death in the United Kingdom, and a blood cancer diagnosis can be life-altering.” While there is currently no cure for this form of blood cancer – chronic myeloid leukaemia (CML) – these findings give hope to the 750 individuals in the UK who are diagnosed with CML each year. Examining how existing medicines can be used to treat other conditions maximises their potential and sheds light on areas where future research can aid CML patients. Blood Cancer UK is committed to developing new therapies for the blood cancer community, which so urgently needs them.
Nature Communications publishes the study titled “Pyruvate anaplerosis is a targetable vulnerability in persistent leukaemic stem cells.” This research was primarily supported by Blood Cancer UK and Cancer Research UK, with additional funding from The Howat Foundation, The Kay Kendall Leukaemia Fund, Tenovus Scotland, and the Friends of the Paul O’Gorman Leukaemia Research Centre.
