Scientists from leading research institutions in five European countries, including the Cancer Research UK Scotland Institute in Glasgow, found that combining a specialised diet with common anti-inflammatory medication could have a noticeable impact on glioblastoma - the most common and one of the deadliest adult brain cancers which is particularly difficult to treat due to its location in sensitive areas of the brain.
The new research, published in Science Advances, uncovered a surprising effect of widely-used steroid medications on how glioblastoma processes vitamins which could lead to new ways to visualise tumours and new treatments.
Dr Saverio Tardito, of the Cancer Research UK Scotland Institute, now of the Center for Cancer Research of the Medical University of Vienna, said:
“We discovered a previously hidden vulnerability in glioblastoma tumours which could lead to new diagnostic and treatment strategies for patients, including diet-based approaches. By combining steroid treatment with dietary strategies that limit the availability of the amino acid methionine we were able to slow tumour growth in preclinical models, pointing to the potential of diet-based interventions to enhance existing therapies”.
Around 12,500 people are diagnosed with a brain, central nervous system or intracranial tumour in the UK each year* including around 1,100 in Scotland.** With only around 1 in 4 people in the UK surviving their disease for 5 years or more, finding new ways to tackle this type of cancer is vital.***
Steroid drugs are potent anti-inflammatory medications routinely prescribed to brain cancer patients to reduce brain swelling and relieve symptoms. While these drugs are essential for patient care, little was previously known about how they influence the internal biochemistry of tumor cells.
In this study, scientists found that steroid medications dramatically altered how glioblastoma cells process vitamin B3, a nutrient normally used by healthy cells to support energy production. Instead of converting a form of vitamin B3, nicotinamide, into an essential key molecule, tumor cells divert it elsewhere. Using advanced techniques, the research team discovered that steroids activate an enzyme called nicotinamide N-methyltransferase which converts vitamin B3 and part of the amino acid methionine into a metabolite only usually present in low levels in the brain (N1-methylnicotinamide).
As a result, glioblastoma tumors accumulate unusually high amounts of this metabolite, about seven times higher than in healthy brain tissue. This distinctive metabolic fingerprint enabled the researchers to develop a new positron emission tomography (PET) imaging approach capable of seeing this change inside tumors. Importantly, the study also shows how this metabolic weakness can be exploited therapeutically. When steroids are administered, reducing the amino acid methionine in a specially designed diet deprives glioblastoma cells of key metabolites they need to grow.
Science engagement lead at Cancer Research UK, Sam Godfrey, said:
“Glioblastoma is a fast-growing cancer with new and better treatments needed urgently. Discoveries which could potentially slow down its growth and provide families with more time are desperately needed. Research like this can lead to the breakthroughs that make a difference to people’s lives and we are delighted to have partly funded this research.”
The study brought together radiochemists, biochemists, cancer biologists, and neurosurgeons working across leading institutions in five European countries: Scotland, Austria, Norway, France, and Luxembourg. By integrating expertise across disciplines and borders, the team was able to move from fundamental metabolic discovery to patient-centered imaging and therapeutic strategies.
The paper, “Steroid-dependent metabolic rewiring reveals novel therapeutic and imaging approaches for glioblastoma” is published in Science Advances and is available here: https://www.science.org/doi/10.1126/sciadv.adx6539
*Based on the average annual number of new cases of brain, other CNS and intracranial tumours (ICD10 C70-C72, C75.1-C75.3, D32-D33, D35.2-D35.4, D42-D43, D44.3-D44.5) diagnosed in the United Kingdom in the years 2018-2019, 2021.
**Based on the average annual number of new cases of brain, other CNS and intracranial tumours (ICD10 C70-C72, C75.1-C75.3, D32-D33, D35.2-D35.4, D42-D43, D44.3-D44.5) diagnosed in Scotland in the years 2018-2019, 2021.