For many people living with isolated lymphatic malformations (LMs) and complex lymphatic anomalies (CLAs), treatment is not a one-time event. Surgery, sclerotherapy, and medications can help manage these benign but complex vascular anomalies, yet many patients require repeated treatments because the abnormal lymphatic vessels can continue to grow or return over time.
That challenge is what drives researchers like Dr. Graham Strub, a surgeon-scientist at the University of Arkansas for Medical Sciences and Arkansas Children's Hospital. His latest research explores a promising new approach that could one day lead to more targeted treatments with fewer side effects.
Why Are Lymphatic Malformations So Difficult to Treat?
Although lymphatic malformations are not cancer, they often develop around important nerves, muscles, and blood vessels, especially in the head and neck. Removing every abnormal cell is not always possible without damaging healthy tissue. As a result, some lesions can continue to grow even after treatment.
Medications such as sirolimus and alpelisib have improved care for many patients by targeting the PI3K signaling pathway, which is commonly activated by mutations in the PIK3CA gene. However, these medications affect cells throughout the body, which can lead to side effects, and not every patient responds the same way.
Researchers are now asking an important question: Can we treat only the abnormal cells while leaving healthy cells alone?
Looking Beyond the Gene
Dr. Strub's laboratory is studying microRNAs—tiny molecules that act like dimmer switches inside our cells. Instead of changing DNA, they help control when certain proteins are made and how cells behave.
Using advanced "multi-omics" technology, his team analyzed genes, proteins, and microRNAs from lymphatic malformation cells to better understand what drives the disease. Rather than identifying a single problem, they found several biological processes working together.
Their research highlighted three key areas:
- Abnormal cell growth, which allows lymphatic malformations to enlarge.
- Inflammation, which may contribute to swelling and ongoing disease activity.
- Tissue remodeling, which helps lesions spread into surrounding tissues.
One microRNA, called microRNA-21, stood out. When researchers blocked it in laboratory-grown LM cells, abnormal cell growth slowed significantly. While these findings are still preclinical, they suggest microRNAs could become promising targets for future therapies.
A Different Way to Deliver Treatment
Perhaps the most exciting part of this research is how these future therapies might be delivered.
Dr. Strub's team is developing microscopic nanoparticles that can carry therapeutic microRNAs directly to lymphatic malformations. Instead of exposing the entire body to medication, these nanoparticles could one day deliver treatment exactly where it is needed.
The long-term vision is even more exciting: a topical cream or ointment that delivers these nanoparticles through the skin to treat certain lymphatic malformations. Although this idea is still in the early stages of research, it represents a completely new way of thinking about treatment—one that could reduce systemic side effects while targeting the disease more precisely.
Why This Research Matters
This work is still in the laboratory, and more research—including animal studies and clinical trials—is needed before these therapies could become available for patients.
Even so, the findings represent an important step toward precision medicine for lymphatic malformations. By understanding the molecular signals that drive abnormal growth, researchers hope to develop treatments that are more personalized, more effective, and easier to tolerate.
For patients and families living with lymphatic malformations, each discovery brings researchers closer to a future where treatment is not only more effective but also less burdensome. While there is still work to do, studies like this continue to build hope for better therapies in the years ahead.
Based on Dr. Graham Strub's presentation for the research network.
