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Take a look at a selection of our recent media coverage:

Discovery of Achilles heel for chronic myeloid leukaemia fuels treatment hope

17th August 2023

A breakthrough in understanding nutrient ‘addictions’ in chronic myeloid leukaemia (CML) cancer cells has led to the discovery of a potential new treatment option for the condition.

Published in the journal Nature Communications, the study, led by the University of Glasgow, focused on identifying the role glucose plays in the behaviour of treatment-resistant CML stem cells.

The researchers found that these cells use glucose to fuel their mitochondria, which protects them from cancer treatments.

To combat this, the researchers successfully targeted the CML stem cells using an investigational drug that prevents them from absorbing glucose, weakening them and potentially making them more susceptible to cancer treatments.

The same drug, MSDC-0160, 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 pursuing a clinical trial to see if combining this drug with current CML treatments would benefit patients.

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, 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.’

Currently, CML is treated with tyrosine kinase inhibitors (TKIs), which limit the advancement of the disease but do not target the CML stem cells directly. Patients must remain on TKIs for the rest of their lives, with associated side effects and the risk of developing resistance to the drugs.

Commenting on the study results, 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… 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.’

CML real-world analysis finds increased second malignancies and comorbidities compared to clinical trials

7th July 2022

Chronic myeloid leukaemia real-world data reveals a higher incidence of second cancers and cardiovascular disease than seen in trials

Real-world registry data on patients with chronic myeloid leukaemia (CML) have revealed a higher incidence of second malignancies and cardiovascular disease among patients than was observed in the original clinical trials. These were the key findings from an analysis by a collaborative group from Spain and the US.

Chronic myeloid leukaemia is a cancer that develops from myeloid blood stem cells. In an analysis of data from 2017, it was estimated that globally, there were an estimated 34,179 incident cases of CML recorded and 24,054 CML-related deaths.

CML is characterised by the presence of the Philadelphia chromosome, which represents the product of a reciprocal translocation between chromosomes 9 and 22 leading to the formation of BCR-ABL1, a tyrosine kinase and which is also a potent oncogene

In 2001, Imatinib an orally administered tyrosine inhibitor was introduced after data showing that the drug was capable of blocking proliferation and inducing apoptosis in CML cell lines.

Imatinib was the first tyrosine kinase inhibitor (TKI) approved for the management of chronic myeloid leukaemia and found to provide an acceptable response in approximately 60% of patients. In fact, after a median follow-up was 10.9 years, patients treated with imatinib had an estimated overall survival rate of 83.3%.

While TKI drugs have significantly improved the treatment for patients with CML, there is limited supportive real-world data on these drugs. As a result, for the present study, researchers sought to better understand not just whether in practice, these drugs improved the survival of patients, but if there were any emergent adverse effects from TKI therapy.

They undertook an analysis of registry data via the TriNetX platform which provided information on CML patients derived from a total of four different cohorts; H120; EMEA Collaborative Network; the US Collaborative Network and the Global Collaborative network.

For each of the four cohorts, the researchers identified a propensity-matched control cohort, i.e., non-CML patients, matched for age and gender. For the analysis, the researchers focused on the development of other malignancies, cardiovascular disease, infections and finally survival.

CML treatment-related outcomes

Using the TriNetX platform enabled the identification of 6133 patients from the four databases. The most commonly prescribed TKI was imatinib followed by dasatinib although other agents used included nilotinib, bosutinib and ponatinib.

When looking at the development of a second malignancy, the H120 had a non-significantly higher incidence compared to the control group (43.9% vs 28.1%, p = 0.079). However, the risk of developing a second malignancy was significantly higher in both the EMEA (odds ratio, OR = 2.61, 95% CI 1.75 – 3.89) and in the US cohort (OR = 8.72, 95% CI 7.96 – 9.55).

In both the EMEA and the US cohort, there was also a statistically higher incidence of cardiovascular disease (EMEA: OR = 1.68, US cohort: OR = 1.88) compared to controls. Moreover, this difference was also significant for each of the different drugs within the TKI class. Fortunately, there were no significant differences between the cohort in relation to infectious diseases.

Finally, there did not appear to be a difference in survival between the CML and non-CML cohorts in any of the four databases.

The authors concluded that while there were similar mortality benefits to the general population among those with CML treated with TKIs, what was of greater concern was the development of both second malignancies and cardiovascular disease.

Citation
Sanz A et al. Outcomes and patterns of treatment in chronic myeloid leukemia, a global perspective based on a real-world data global network Blood Cancer J 2022

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