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Modifying The Inflammasome To Treat Malignant Mesothelioma

Arti Shukla, Ph.D.
University of Vermont College of Medicine
R01ES021110

Chemotherapeutic drugs coupled with an inhibitor to reduce specific tumor-promoting components may play a beneficial role in malignant mesothelioma treatment, according to new research funded by NIEHS. Malignant mesothelioma, a type of cancer, is caused by exposure to asbestos, and inflammation plays an important role in its development. The drugs target the inflammasome, which is responsible for the activation of inflammatory processes in the body.

In human cell lines and tissue, researchers found that chemotherapeutic drugs elevate the levels of two components of the inflammasome that contribute to cell death — NLRP3 and caspase-1 — playing a beneficial role in malignant mesothelioma therapy. However, the drugs also increased the levels of pro-inflammatory molecules that promote tumor growth , most importantly interleukin-1-beta.

Based on these findings, they conducted cell line and mouse studies focusing on the effects of the inflammasome. They combined the chemotherapeutic drugs with a drug that inhibits interleukin-1 receptors, in an attempt to block the negative effects of inflammasome activation. The mouse studies showed that tumors were smaller in the combined treatment group compared to the group just treated with chemotherapeutics or untreated groups.

Taken together, the study’s findings provide the first step toward a possible strategy for inhibiting malignant mesothelioma growth using a combination of chemotherapeutics with interleukin-1 receptor agonists.

Citation: Westbom C, Thompson JK, Leggett A, MacPherson M, Beuschel S, Pass H, Vacek P, Shukla A. 2015. Inflammasome modulation by chemotherapeutics in malignant mesothelioma. PLoS ONE 10(12): e0145404.


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