University of Cambridge researchers have discovered that metformin, a common diabetes medication taken by millions worldwide, may offer unexpected protection against acute myeloid leukemia (AML), an aggressive form of blood cancer that kills approximately four out of five patients within five years of diagnosis.
The groundbreaking study, published in the journal Nature, reveals that metformin could disrupt the disease process in individuals with genetic predispositions to AML, potentially opening new pathways for cancer prevention.
Targeting Genetic Mutations
The research focused on mutations in the DNMT3A gene, which are linked to 10-15% of AML cases. Scientists found that metformin could interfere with how pre-cancerous cells produce energy, effectively halting their development into leukemia. The drug also appears to help reverse some of the damage caused by the faulty DNMT3A gene.
"Blood cancer poses unique challenges compared to solid cancers like breast or prostate, which can be surgically removed if identified early," explained Professor George Vassiliou from the Cambridge Stem Cell Institute, who co-led the research. "With blood cancers, we need to identify people at risk and then use medical treatments to stop cancer progression throughout the body."
Human Data Supports Laboratory Findings
After initial discoveries in laboratory experiments with mice, the researchers examined health records from more than 412,000 UK Biobank participants. Their analysis revealed that individuals taking metformin were less likely to show changes in the DNMT3A gene. This association persisted even after accounting for other potential influencing factors such as diabetes or body mass index.
The findings provide compelling evidence that metformin could potentially be repurposed as a preventive treatment for those at high risk of developing AML. Currently, while genetic screening can identify individuals with increased risk, there are no preventive treatments available.
Advantages of Drug Repurposing
Metformin has been used for decades to treat diabetes and has an established safety profile with minimal side effects. It costs the NHS just 35p per pill, making it an affordable option if proven effective for cancer prevention.
Dr. Rubina Ahmed, Director of Research at Blood Cancer UK, which part-funded the study, highlighted the advantages of drug repurposing: "Repurposing safe, widely available drugs like metformin means we could potentially get new treatments to people faster, without the need for lengthy drug development pipelines."
Moving Toward Clinical Trials
While the results are promising, experts emphasize that clinical trials are necessary to confirm metformin's effectiveness in preventing AML in high-risk patients.
"It's important that we work to find new ways to slow down or prevent AML in people at high risk," said Tanya Hollands from Cancer Research UK, another funder of the research. "While this early-stage research is promising, clinical trials are now needed to find out if this drug could benefit people."
The Cambridge team is already preparing clinical trials targeting patients identified as having changes to their DNMT3A gene that increase their risk of developing AML.
AML: A Difficult-to-Treat Cancer
Approximately 3,100 people are diagnosed with AML each year in the UK. The disease progresses rapidly and is particularly challenging to treat because, unlike solid tumors, there is no localized mass that can be surgically removed.
Symptoms of AML can be difficult to detect as they resemble general illness, including fatigue, high temperature, repeated infections, easy bruising and bleeding, breathlessness, unintended weight loss, swollen lymph nodes, bone pain, stomach pain, and pallor. Current treatment primarily consists of chemotherapy, with limited effectiveness.
The potential repurposing of metformin represents a significant step forward in the prevention of this deadly blood cancer, offering hope to those at high genetic risk of developing the disease.
