Lung cancer remains one of the deadliest cancers in the world.
Smoking is its biggest cause, but people who have never smoked can also develop the disease because of factors such as air pollution, secondhand smoke, workplace exposures, genetics, and other changes in the lungs.
Scientists at MIT are now exploring an unusual way to fight lung cancer: stopping it before a tumor fully develops. Their new study suggests that reducing a certain type of inflammation in the lungs could make it harder for early tumors to form.
The research was led by scientists at the Massachusetts Institute of Technology, with Sangeeta Bhatia as senior author and Cathy Wang as lead author. The study was published in the journal Science Advances.
The team focused on an enzyme called caspase-1. Enzymes are proteins that help chemical processes happen inside the body, and caspase-1 has an important role in inflammation, which is the immune system’s response to injury, infection, or other threats.
Inflammation is normally useful because it helps the body defend and repair itself. But when inflammation continues for too long, it can damage tissue and create conditions that may support the growth of cancer.
The researchers became interested in this idea partly because of an earlier large clinical trial called CANTOS. That trial was originally testing an anti-inflammatory medicine for heart disease, but researchers unexpectedly noticed fewer cases of lung cancer among some people receiving the treatment.
The medicine used in CANTOS blocked IL-1 beta, a substance made by the immune system that helps drive inflammation. Later studies did not show the same benefit in people who already had established lung cancer, suggesting that reducing inflammation might be more useful before cancer becomes advanced.
The MIT team wanted to understand what was happening earlier in this process. They used specially designed sensors that can detect the activity of enzymes inside tissues and tested them in mice genetically designed to have a high risk of developing lung tumors.
The researchers activated cancer-related changes in the mice and then studied the lungs before obvious tumors had fully formed. Some mice received a treatment that blocked IL-1 beta, while others received no treatment.
The experiments showed that caspase-1 was highly active in the mice that went on to develop lung tumors. Its activity was much lower in mice treated with the IL-1 beta blocker, which also developed fewer tumors.
Importantly, active caspase-1 was found mainly in tumor tissue rather than nearby healthy lung tissue. The researchers also examined a small number of human lung-fluid samples and found more caspase-1 activity in samples from people with lung cancer than in samples from healthy people with a similar smoking history.
The team then asked whether directly blocking caspase-1 could prevent tumors. They treated high-risk mice before tumors developed using a caspase-1-blocking drug, an IL-1 beta-blocking antibody, or both treatments together.
Mice receiving either treatment alone developed fewer and smaller tumors than untreated mice. When the two treatments were combined, nearly 20% of the mice did not develop tumors at all during the experiment.
The caspase-1 drug is especially interesting because drugs of this type have already been tested in people for conditions such as rheumatoid arthritis. Unlike antibody treatments that may require an injection or infusion, a caspase-1 inhibitor could potentially be taken by mouth.
That does not mean people at risk of lung cancer can take this medicine today. The evidence is mainly from mice, the human sample analysis was small, and researchers still need clinical trials to learn whether the approach can actually prevent lung cancer safely in people.
Still, the study supports a growing idea known as cancer interception. Instead of waiting for a dangerous tumor to appear and then treating it, doctors might one day identify people at especially high risk and interrupt the biological changes that allow cancer to begin.
The results are promising because they identify both a possible warning signal and a possible treatment target. Caspase-1 activity might help researchers identify harmful inflammation, while blocking the enzyme could potentially reduce the chance that this inflammation helps early lung tumors grow.
The biggest unanswered question is whether the strong effects seen in specially designed mice will translate to humans. If future trials confirm the findings, repurposing an already studied drug could shorten part of the long path toward a preventive treatment, but careful testing will be essential before doctors know who should receive it and whether the benefits outweigh the risks.
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