Obesity can act as fuel for leukaemia, according to a study led by Indiana University School of Medicine scientists.

To help many patients facing aggressive blood cancers overcome this metabolic risk, researchers identified a potential new treatment strategy that combines popular weight-loss medications with anti-inflammatory drugs.

The findings were recently published in the Journal of Clinical Investigation.

While obesity is known to increase the risk of certain blood cancers, the researchers sought to determine exactly how the chronic condition changes the body to help leukaemia thrive.

"This study presents a fundamentally new understanding of how metabolic disease — specifically obesity — can directly influence the initiation and progression of leukaemia," said Reuben Kapur, PhD, director of the IU School of Medicine Herman B Wells Centre for Paediatric Research and an equal first author of the study.

"Rather than treating obesity as a passive risk factor, the work establishes it as an active biological driver linking metabolism, inflammation and cancer."

After analysing electronic health record data from more than 440,000 people in the UK Biobank and conducting experiments in mouse models, the researchers discovered that obesity creates a state of chronic inflammation that accelerates the growth of mutated, leukaemia-causing blood stem cells.

This harmful environment is marked by high levels of an inflammatory molecule called IL-17A and a decrease in the body's natural GLP-1 metabolic signalling.

Notably, both pathways can be targeted with readily available medications.

In the study, the scientists tested a dual-therapy approach involving anti–IL-17A antibodies, which are currently used to treat autoimmune diseases, and drugs that boost GLP-1 signalling, which are used in several popular diabetes and weight-loss medicines.

They found that combining an IL-17A blocker with a GLP-1 drug successfully lowered the amount of leukaemia and improved immune function in obese mice.

"Because these therapies are already available and have established safety profiles, our results raise the possibility of repurposing them either alone or in combination to improve outcomes for patients with high-risk myeloid leukemias," said Santhosh K. Pasupuleti, PhD, assistant research professor of paediatrics at the IU School of Medicine and co-senior author of the study.

"This strategy could help reduce leukaemia progression while simultaneously improving metabolic health and restoring anti-tumour immunity."

The team expects to evaluate the new therapeutic approach in clinical studies to further determine whether combining IL-17A inhibitors with GLP-1 drugs can safely and effectively benefit patients with obesity-associated leukaemia.

Future studies will also focus on identifying which patients are most likely to benefit from this treatment and explore how it may translate to other forms of cancer.

"The broader significance of this work extends beyond leukaemia," Kapur said.

"The demonstration that metabolic dysfunction can reprogram immune responses to promote cancer progression has implications for multiple malignancies and suggests that metabolic interventions could become a foundational component of cancer prevention and therapy."

Source: Indiana University