A drug that has sat in millions of medicine cabinets for decades may turn out to be a powerful ally in the fight against some of the most treatment-resistant cancers. New research from Northwestern University in Illinois has shown that montelukast — better known by the brand name Singulair, and prescribed for asthma and allergies since the late 1990s — can help the immune system attack tumors that normally shrug off immunotherapy.
The findings, published in Nature Cancer, center on a molecule called CysLTR1. It is best known for its role in inflammation and allergic asthma, which is why montelukast was designed to block it. What Northwestern's team discovered is that many cancers exploit the same molecule to weaken the body's defenses. By switching CysLTR1 off, the researchers slowed tumor growth, restored immune function, and even revived treatment response in cancers that had stopped responding altogether.
How Tumors Hijack the Immune System
To grow and spread, aggressive tumors recruit a type of white blood cell called neutrophils. Normally neutrophils help fight infection, but cancer twists their role, turning them into accomplices that suppress the immune response. The Northwestern team, led by Professor Bin Zhang at the Feinberg School of Medicine, traced this hijack to CysLTR1 acting as an on/off switch.
"When we turned off this switch, either genetically or with existing drugs, we not only slowed tumor growth, but also helped the immune system recover its ability to fight the cancer," Zhang said.
The team tested the idea across mouse models of triple-negative breast cancer, melanoma, ovarian cancer, colon cancer, and prostate cancer. In every case, blocking CysLTR1 — either by genetic deletion or with drugs like montelukast — improved outcomes. Tumors grew more slowly, survival lengthened, and animals that had stopped responding to immunotherapy began responding again.
Reprogramming the Body's Own Cells
What makes the result especially striking is that the drug did not simply destroy the rogue neutrophils. It re-educated them. "Importantly, instead of simply removing these harmful white blood cells, we were able to reprogram them into cells that support immune attack," Zhang explained. "That means we're not just targeting the cancer, we're re-training one type of abundant immune cells in the body to fight the tumor again."
The researchers also analyzed human immune cells and tumor samples, plus large cancer patient datasets, and saw the same patterns. Patients whose tumors showed higher CysLTR1 activity tended to fare worse, suggesting the pathway is at work in real-world disease.
A Fast Path to the Clinic
One of the most exciting aspects of the discovery is how quickly it could move forward. Montelukast is already approved by the U.S. Food and Drug Administration, widely available as a generic, and has decades of safety data behind it. That dramatically lowers the bar for clinical testing compared with developing a new molecule from scratch.
Drug repurposing — finding new uses for existing medicines — has become an increasingly important strategy in oncology, where the road from lab to approval typically stretches more than a decade. By matching an old pill to a newly understood biological mechanism, researchers can leapfrog years of preliminary safety work and go straight to testing whether the combination helps patients.
The Northwestern team is now planning clinical trials to see whether adding montelukast to immunotherapy regimens can push response rates higher in cancers like triple-negative breast cancer, where treatment options remain limited.
A Reminder That Discovery Is Cumulative
The story also underlines how progress in biology often comes from connecting fields that seem unrelated. Decades of research on asthma, an inflammatory airway disease, produced a safe, well-understood drug. Decades of cancer immunology revealed the central role of neutrophils. Joining the two threads opened a door no one was looking for.
For patients facing tough cancers, the result is genuine hope from a familiar source — a small white pill that may soon do far more than ease an allergy attack.
