Lung cancer remains one of the deadliest cancers in the United States, claiming more than 100,000 lives each year. Cigarette smoking is the dominant risk factor, but the disease also develops in people who have never smoked and in individuals exposed to pollutants, workplace hazards, or chronic inflammation. Now, researchers at the Massachusetts Institute of Technology report that blocking a key inflammatory enzyme may prevent lung tumors from emerging, raising the possibility of using an existing drug as a form of cancer prevention rather than waiting until disease is detectable.

The enzyme, caspase-1, helps activate one of the body’s most important inflammatory signals, a molecule known as interleukin-1 beta, or IL-1β. In a study published in Science Advances, the MIT team found that caspase-1 was strongly active in early lung tumors in mice. When the researchers treated animals with a small-molecule caspase-1 inhibitor, tumor development was substantially reduced. The findings suggest that inflammation is not merely a consequence of tumor growth but may help create the biological conditions that allow cancerous cells to survive and expand.

“This concept is called cancer interception,” says Sangeeta Bhatia, a senior author of the study and an MIT professor whose research focuses on cancer biology, nanotechnology, and medical engineering. The idea is to identify people who are especially likely to develop cancer and intervene before malignant growth becomes established. For lung cancer, such a strategy could be particularly valuable because tumors can evolve silently for years before symptoms appear. A preventive medicine that could be taken orally might eventually complement existing screening methods, especially for people at elevated risk.

The new work builds on an unexpected observation from the CANTOS clinical trial, which was originally designed to test whether reducing inflammation could prevent heart attacks and strokes. In 2017, investigators reported that patients receiving canakinumab, an antibody that blocks IL-1β, also experienced fewer diagnoses of lung cancer in a subset of the trial population. Later studies showed that blocking IL-1β was not an effective treatment for people with established lung cancer, but the earlier results suggested that suppressing inflammation before tumors become advanced might be a different and more promising strategy.

IL-1β is produced in an inactive form and must be cleaved by a protease before it can trigger inflammation. Caspase-1 is one of the enzymes capable of performing this molecular cut. It is activated within a cellular structure called the inflammasome, which functions as an immune surveillance system. When the inflammasome detects signs of cellular damage or infection, caspase-1 becomes active and processes IL-1β into its mature form. The released cytokine can then stimulate immune cells, alter tissue behavior, and promote the inflammatory environment surrounding a developing tumor.

To determine which proteases were active during the earliest stages of lung cancer, the MIT researchers adapted nanosensors developed in Bhatia’s laboratory. These sensors are built from nanoparticles coated with short protein fragments called peptides. When a specific protease cuts a peptide, the resulting molecular fragments can be detected in biological samples, creating a readout of enzyme activity. Unlike a conventional biopsy, which provides a snapshot of a small area of tissue, the nanosensors can reveal biochemical activity across an organ and may help identify disease-associated processes before tumors are large enough to be seen.

The team tested the sensors in a genetically engineered mouse model known as KPS. These mice carry inducible cancer-causing mutations in the tumor-suppressor gene p53 and the oncogene Kras, two genetic alterations frequently associated with human lung cancer. The animals also express a peptide called SIINFEKL, which helps stimulate T-cell activity and inflammation in the lungs. Five weeks after the cancer-associated mutations were activated, before tumors could be readily detected, some mice received an antibody that blocked IL-1β. Three weeks later, the researchers measured protease activity in the lungs.

In untreated animals, all of which developed lung tumors, caspase-1 activity was particularly high. The enzyme’s activity was concentrated within tumor tissue rather than in nearby healthy lung, suggesting that it was linked to the developing malignancy rather than simply reflecting generalized inflammation. Mice treated with the IL-1β-blocking antibody developed fewer tumors, and their caspase-1 activity was significantly lower. The researchers also examined a small collection of human lung-fluid samples in collaboration with Lecia Sequist of Harvard Medical School and Mass General Brigham. Patients with lung cancer had higher caspase-1 activity than healthy donors, even though the groups had similar smoking histories.

The researchers next asked whether directly blocking caspase-1 could reproduce or improve the effects of IL-1β inhibition. Before tumors formed, at-risk mice received a caspase-1 inhibitor, the IL-1β antibody, both treatments, or no treatment. Animals given either drug alone developed tumors that were smaller and less numerous than those in untreated mice. The combination produced the strongest result: nearly 20 percent of the mice receiving both drugs never developed tumors at all. Because caspase-1 inhibitors are small molecules that can be taken orally, they may offer practical advantages over antibody treatments, which generally require intravenous administration.

The inhibitor used in the research has already been tested in human clinical trials for rheumatoid arthritis and other inflammatory diseases, meaning that some safety and dosing information may already be available. That does not establish that the drug is safe or effective for cancer prevention, however. Preventive treatments are given to people who may be healthy for many years, so their benefits must clearly outweigh potential side effects. The researchers say future trials could focus on individuals with a high probability of developing lung cancer and use molecular biomarkers to identify those most likely to benefit from suppressing the IL-1β pathway.

The findings also illustrate how cancer prevention may increasingly depend on mapping the biological events that precede visible tumors. By combining protease-sensitive nanosensors, genetically engineered models, human samples, and existing anti-inflammatory compounds, the MIT team identified caspase-1 as a possible intervention point in early lung cancer. Much more work is required before such treatment could become part of medical practice, including larger studies in humans and careful assessment of long-term immune effects. Still, the results point toward a future in which cancer risk is detected early enough for inflammation to be interrupted before it helps transform vulnerable lung cells into tumors.

Subject of Research: Caspase-1 activity, IL-1β-mediated inflammation, and prevention of early lung cancer development

Article Title: Multimodal profiling of proinflammatory protease activity identifies caspase-1 as a target for lung cancer interception

News Publication Date: 14-Aug-2026

Web References: https://doi.org/10.1126/sciadv.adz4263

References: MIT researchers; Science Advances; CANTOS clinical trial; Sangeeta Bhatia; Cathy Wang; Lecia Sequist; Tyler Jacks; Swanton laboratory at the Francis Crick Institute

Keywords: lung cancer, cancer prevention, cancer interception, caspase-1, IL-1β, inflammation, proteases, inflammasome, nanosensors, precision medicine, cancer research, MIT

Tags: cancer interception strategiescaspase-1 inhibitor therapyearly detection of lung tumorsIL-1β in tumor growthinflammation-driven carcinogenesisinflammatory enzyme caspase-1lung cancer preventionnon-smoking related lung cancer risk factorspotential for existing drugs in cancer preventionpreclinical studies on lung cancerrole of inflammation in cancer developmenttargeted inflammation suppression in cancer treatment