Common asthma drug may turn off tumor 'switch' tied to immunotherapy resistance

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by Northwestern University

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A drug widely used to treat asthma and allergies may also help fight aggressive cancers, reports a new Northwestern Medicine study that uncovered how tumors hijack common white blood cells to evade immunotherapy.

The findings in mice and human tissues point to a practical, new way to improve treatment for tough tumors, such as triple-negative breast cancer, where immunotherapy often fails.

The study is published in Nature Cancer.

At the center of the discovery is a molecule called CysLTR1, which is best known for its role in asthma and inflammation. Drugs that block it, such as montelukast (also called Singulair), have been prescribed for decades to treat asthma.

In this study, the Northwestern scientists found that many cancers exploit CysLTR1 to resist treatment. Specifically, the scientists found that tumors trick the immune system into helping them grow by increasing a group of white blood cells called neutrophils. And this process, they discovered, is controlled by the CysLTR1 molecule, which acts 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," said study senior author Dr. Bin Zhang, the Johanna Dobe Professor of Cancer Immunology at Northwestern University Feinberg School of Medicine.

How the study was conducted

Zhang and colleagues combined experiments in mouse models, human immune cells and human tumor samples with analysis of large patient cancer datasets.

The mouse studies included models with triple-negative breast cancer, melanoma, ovarian cancer, colon cancer and prostate cancer. The scientists either genetically removed CysLTR1 or blocked it using drugs such as montelukast.

In several mouse models, blocking the pathway slowed tumor growth, improved survival and restored response to immunotherapy. That worked even in tumors that had already stopped responding to treatment.

Zhang's team also analyzed human immune cells and found, again, that blocking CysLTR1 prevented the formation of immune-suppressing neutrophils.

"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."

Finally, in analyses of human tumor samples and public cancer datasets, the scientists found more evidence that CysLTR1 plays a crucial role in promoting cancer growth. They found that patients with higher CysLTR1 activity tended to have worse survival and poorer response to immunotherapy across multiple cancer types.

Clinical trials

Because drugs that block CysLTR1, such as montelukast, are already FDA-approved, the findings could quickly move into patient trials.

"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," Zhang said.

"The next steps are to confirm this mechanism in patients, identify who will benefit most, optimize how we use these drugs especially in combination with immunotherapy, and begin carefully designed clinical trials," he added.

Publication details

Targeting cysteinyl leukotriene receptor 1 reprograms tumor-promoting myelopoiesis and overcomes immune checkpoint therapy resistance, Nature Cancer (2026). DOI: 10.1038/s43018-026-01174-7

Journal information: Nature Cancer

Key medical concepts

Cancer ImmunotherapymontelukastTriple-Negative Breast CarcinomaNeutrophils

Clinical categories

Oncology Provided by Northwestern University Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

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