Researchers at Northwestern University's Feinberg School of Medicine have discovered that montelukast—the asthma drug millions know as Singulair—may become a powerful ally in the fight against aggressive cancers that have resisted standard immunotherapy. The finding emerged from experiments in mice and human tissues, revealing how tumors exploit a molecular on/off switch to disable the immune system's cancer-fighting abilities.
The breakthrough hinges on understanding a molecule called CysLTR1, long known for its role in asthma and inflammation. Tumors hijack this molecule to trick the body into producing more neutrophils, white blood cells that suppress immune response. By blocking CysLTR1 with existing asthma medications, the Northwestern team found they could not only slow tumor growth but essentially reprogram these harmful immune cells into cancer fighters.
"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," said Professor Bin Zhang, the study's senior author. His team combined experiments across multiple approaches: mouse models with triple-negative breast cancer, melanoma, ovarian cancer, colon cancer, and prostate cancer; human immune cells in the lab; and analysis of large patient cancer datasets.
In the mouse studies, blocking CysLTR1—either by removing it genetically or using drugs like montelukast—consistently slowed tumor growth and improved survival. Remarkably, the approach worked even in tumors that had already stopped responding to immunotherapy. The researchers also examined human immune cells directly, and their findings, published in the journal Nature Cancer, again confirmed that blocking CysLTR1 prevented the formation of immune-suppressing neutrophils. Rather than simply removing these cells, the team discovered they could retrain them to support immune attack against cancer.
Analysis of human tumor samples and public cancer datasets provided further validation. Patients with higher CysLTR1 activity tended to have worse survival and poorer response to immunotherapy across multiple cancer types. This pattern held true for aggressive forms like triple-negative breast cancer, where new treatment options remain urgently needed.
What makes this discovery particularly compelling is its practical timeline. Unlike drugs still in early development, montelukast and other CysLTR1-blocking medications are already FDA-approved and prescribed safely to millions of asthma and allergy patients worldwide. This means the findings could move relatively quickly from laboratory to patient trials. Professor Zhang emphasized the pathway forward: "We may be able to quickly and safely test it in cancer patients to improve immunotherapy, especially in aggressive cancers, like triple-negative breast cancer, where new options are urgently needed."
The next phase involves confirming these mechanisms in human patients, identifying which patients will benefit most, and optimizing how these drugs work in combination with existing immunotherapy. Carefully designed clinical trials will follow. By repurposing a medication already proven safe in chronic use, researchers hope to unlock a new strategy for cancers that have proven stubbornly resistant to current treatments—offering hope to patients for whom options have been limited.