Chicago scientists at Northwestern Medicine say a common asthma pill may have a surprising second act: helping tough-to-treat cancers respond to immunotherapy, at least in lab models. In new research, the team reports that a widely prescribed drug appeared to slow tumor growth and help tumors once again react to immune-based treatments. The key, they say, is a molecular "switch" that cancers use to summon neutrophils that shield malignant cells from immune attack. When that pathway was blocked, those same cells were reprogrammed to support anti-tumor immunity. The study, published today, points to the possibility of testing montelukast (Singulair), an already approved leukotriene-receptor antagonist, as an add-on to checkpoint inhibitors for aggressive tumors such as triple-negative breast cancer.
How the drug flips a tumor 'switch'
In a paper in Nature Cancer, investigators trace how STAT3 activity drives the induction of cysteinyl leukotriene receptor 1 (CysLTR1) during "emergency" myelopoiesis, a process that churns out immunosuppressive neutrophils. The authors report that either genetically deleting CysLTR1 or blocking it with drugs shrinks the pool of these tumor-promoting cells, slows the pace of tumor growth, and restores sensitivity to anti-PD-1 therapy across mouse models of triple-negative breast, melanoma, ovarian, colon, and prostate cancers.
Already-approved drug could move into trials
Because drugs that block CysLTR1, most notably montelukast, already have FDA approval, the researchers note that the path to early clinical testing could be shorter than for an entirely new compound. Montelukast first won approval in 1998, but the FDA has since required a boxed warning about rare neuropsychiatric side effects, a risk that would have to be weighed carefully in any cancer trial. Early-stage studies that incorporate montelukast into cancer-related protocols are already listed on ClinicalTrials.gov.
Chicago team cautious but optimistic
According to Northwestern University, the next steps include confirming that the same mechanism is at work in patients, figuring out which patients stand to benefit the most, and, as study senior author Bin Zhang put it, to "begin carefully designed clinical trials." "We may be able to quickly and safely test it in cancer patients to improve immunotherapy," Zhang said. Local coverage by FOX 32 Chicago features an interview with Zhang discussing the findings.
Experts stress that promising lab work does not automatically translate into effective treatments in the clinic, and that patients should not attempt to self-medicate with montelukast for cancer outside of a formal study. The FDA drug-safety communications and current prescribing information underscore the known risks and the importance of medical supervision whenever montelukast is used, especially off-label.
