MIT News breed · Wetenschap

Drug targeting inflammatory enzyme shows promise in preventing lung cancer

MIT researchers have found that blocking an enzyme called caspase-1, which is involved in lung inflammation, appears to reduce the risk of developing lung tumors in mice. This enzyme is active in developing tumors, and inhibiting it significantly lowered tumor development. The drug used to inhibit caspase-1 has already undergone clinical trials for other conditions, raising hopes for its use as a preventative treatment for high-risk individuals.

Lung cancer causes over 100,000 deaths annually in the U.S., with smoking being the primary risk factor, though environmental exposures also contribute. The study suggests that targeting caspase-1, an enzyme active in developing lung tumors in mice, could prevent some of these deaths. When mice were treated with a drug that inhibits caspase-1, their likelihood of developing lung tumors decreased.

The researchers are hopeful about testing this drug, which has already entered clinical trials for other diseases, as a preventative measure for people at elevated risk for lung cancer. This approach, known as cancer interception, could potentially benefit millions by offering preventative medicine to high-risk individuals identified through testing.

Previous research hinted that targeting lung inflammation might prevent lung cancer. A clinical trial involving an anti-inflammatory drug that blocks the cytokine IL-1 beta unexpectedly showed lower lung cancer rates in a subset of participants. While this antibody had limited effect on established lung cancer, its potential for preventing progression in high-risk patients is still being explored.

The MIT team investigated if proteases, enzymes that cleave other proteins, might be involved in the inflammatory pathway linked to IL-1 beta. Their lab has developed diagnostic nanosensors to track protease activity, which can contribute to cancer development and inflammation. These sensors revealed that caspase-1 was highly active in untreated mice that developed lung tumors, but significantly less active in treated mice with fewer tumors.

Analysis of a small number of human lung fluid samples also indicated higher caspase-1 activity in lung cancer patients compared to healthy donors. The researchers then tested caspase-1 inhibitors, along with IL-1 beta antibodies, in at-risk mice. Combining both treatments resulted in nearly 20 percent of mice never developing tumors, while individual treatments led to smaller and fewer tumors than in untreated mice.

Caspase-1 inhibitors offer an advantage over antibodies as they can be taken orally and have already been tested in human clinical trials for conditions like rheumatoid arthritis. This existing safety data makes the drug an attractive candidate for repurposing as a cancer preventative treatment.

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