Most cancers begin with small changes in our DNA that build up over time. As we age, these genetic mutations can quietly accumulate, increasing the risk of cancer and other serious diseases long before any symptoms appear.
This is especially true for blood-forming, or hematopoietic, stem cells – the “master” cells that produce all our blood cells. In up to one in three people over 60, these stem cells acquire mutations that allow them to grow faster than normal. This condition, known as clonal hematopoiesis (CH), often goes unnoticed, but it significantly increases the risk of developing blood cancers like leukemia, as well as other age-related and inflammatory diseases like heart attacks and stroke.
Supported by $2 million from the Terry Fox Research Institute as part of a major cancer prevention initiative led by the Canadian Institutes of Health Research, a collaborative team of researchers will spend the next five years exploring whether medications already being used to treat diabetes could help prevent or slow the progression of clonal hematopoiesis into cancer.
The team will investigate whether GLP-1 receptor agonists – a class of drugs that includes Ozempic and has transformed the treatment of diabetes and obesity – can be repurposed to suppress the inflammation that fuels the growth of mutated stem cells.
Recent studies have revealed a complex relationship between clonal hematopoiesis, inflammation and diabetes wherein mutated blood stem cells produce inflammatory signals, creating inflammation that, in turn, further accelerates the growth of abnormal cells. This vicious cycle appears to be worse in people with diabetes.
However, diabetes medications may help disrupt this process. In fact, the team has shown that metformin, one of the most commonly used diabetes drugs, can help control the growth of mutated blood stem cells. While other studies suggest that people taking GLP-1 receptor agonists may have a lower risk of developing blood cancers.
In this project, the team will combine laboratory studies in mouse models with analyses of patient blood samples to better understand how GLP-1 receptor agonists affect mutated stem cells and their inflammatory responses. They will also examine blood samples from patients already taking these medications to assess whether GLP-1 therapy influences the presence and severity of clonal hematopoiesis.
“Funding prevention-focused research like this is critical,” says Dr. Steven Chan, one of the project’s leaders and a senior scientist and staff physician at the Princess Margaret Cancer Centre. “If we can intervene early, before a pre-cancerous condition becomes a malignancy, we have the potential to spare patients from devastating diagnoses altogether.”
This research brings together an interdisciplinary team spanning the Princess Margaret Cancer Centre, the Lunenfeld-Tanenbaum Research Institute and three Toronto hospital sites. It is co-led by Dr. Stephanie Xie, a leader in human blood stem cell biology who recently discovered a novel inflammatory stem cell population linked to clonal hematopoiesis, and Dr. Daniel Drucker, whose pioneering work on GLP-1 biology helped lay the foundation for the drugs being studied.
By building the evidence needed for future clinical trials and exploring the potential of drugs that are already approved for use, the team hopes to inform and accelerate new prevention approaches for clonal hematopoiesis and related cancers.
“We are deeply grateful to the Terry Fox Foundation donors whose generosity makes this kind of ambitious, team-based research possible,” says Dr. Chan. “It's especially exciting because our project bridges laboratory science with a real-world clinical study, giving us the opportunity to translate discoveries directly into a potential prevention strategy for patients.”