Asthma Drug Montelukast Shows Promise in Overcoming Cancer Immunotherapy Resistance
Key Insights
Northwestern Medicine researchers discovered that montelukast, a widely-used asthma (search) medication, can restore immunotherapy sensitivity in treatment-resistant cancers by blocking the CysLTR1 (search) receptor.
The study found that tumors hijack CysLTR1 (search) to reprogram neutrophils into immunosuppressive cells, effectively shielding cancer from immune attack.
In preclinical models of triple-negative breast cancer (search) and other aggressive cancers, montelukast slowed tumor growth and improved survival when combined with immunotherapy.
A common asthma (search) medication taken by millions worldwide may hold the key to overcoming one of cancer immunotherapy's greatest challenges: treatment resistance. Researchers at Northwestern Medicine in Chicago have discovered that montelukast, sold under the brand name Singulair, can restore immunotherapy sensitivity in aggressive cancers that typically don't respond to immune-based treatments.
The study, published in Nature Cancer, reveals how tumors exploit a molecular pathway originally designed for lung inflammation to evade immune attack. This discovery could have profound implications for cancer treatment, particularly in countries like India where access to experimental therapies remains limited.
Targeting the Immune Escape Mechanism
The Northwestern team identified CysLTR1 (search), the same receptor that montelukast blocks in asthma (search) treatment, as a critical component in cancer's immune evasion strategy. In healthy lungs, CysLTR1 manages inflammation, but tumors have learned to hijack this pathway for a more sinister purpose.
"When we turned off this switch, either genetically or with existing drugs, we not only slowed tumour growth, but also helped the immune system recover its ability to fight the cancer," said Dr. Bin Zhang, the study's senior author and Professor of Cancer Immunology at Northwestern University Feinberg School of Medicine.
The research revealed that tumors use CysLTR1 (search) to recruit and reprogram neutrophils—normally part of the body's front-line immune defenses—into cells that actively protect cancer from immune attack. These corrupted neutrophils suppress the immune response, essentially turning the body's own soldiers against it.
Preclinical Evidence Across Multiple Cancer Types
The research team employed multiple approaches, including mouse models of triple-negative breast cancer (search), melanoma (search), ovarian, colon, and prostate cancer (search), along with analysis of human immune cells, tumor samples, and large public cancer datasets.
In the preclinical models, blocking CysLTR1 (search) either genetically or through montelukast administration slowed tumor growth, improved survival, and restored sensitivity to immunotherapy. Notably, the effect persisted even in tumors that had already stopped responding to treatment.
The mechanism proved particularly intriguing: rather than simply reducing harmful neutrophils, montelukast reprogrammed them, converting immunosuppressive cells into ones that actively supported the immune attack on cancer. Analysis of human tumor samples reinforced these findings, showing that patients with higher CysLTR1 (search) activity had worse survival outcomes and poorer responses to immunotherapy across multiple cancer types.
Addressing India's Cancer Treatment Gap
The implications extend far beyond the laboratory, especially for India's healthcare landscape. Triple-negative breast cancer (search) accounts for 20-31% of all breast cancer cases in India—significantly higher than in Western countries—and predominantly affects younger, pre-menopausal women. Approximately 100,000 women receive this diagnosis annually, with five-year survival rates in metastatic cases remaining below 30%.
Access to newer, experimental therapies remains limited outside major urban centers, and cost presents a significant barrier even where treatments are available. Montelukast offers a stark contrast: it's already approved by regulatory bodies including the US Food and Drug Administration, has decades of safety data, and generic versions are inexpensive and widely manufactured.
This represents drug repurposing—finding new clinical uses for medicines already proven safe in humans—which carries a practical advantage over entirely new molecules: a considerably shorter pathway to clinical trials.
Next Steps and Clinical Translation
The researchers emphasize that these findings come from animal models and human tissue analyses, not clinical trials involving cancer patients. They frame the results as a promising early signal rather than a confirmed treatment.
"The next steps are to confirm this mechanism in patients, identify who will benefit most, optimise how we use these drugs—especially in combination with immunotherapy—and begin carefully designed clinical trials," Dr. Zhang explained.
The study opens a genuinely exciting avenue for cancer treatment. The possibility that a drug millions already take safely every day might, in carefully designed combinations with immunotherapy, help re-sensitize tumors that have learned to hide from the immune system represents the kind of finding that can shift research directions.
While the timeline for clinical translation depends on upcoming trials, the scientific rationale and motivation to move quickly have rarely been clearer, particularly given the urgent need for accessible cancer treatments in resource-limited settings.