Health
Statin therapy may prevent cancer by inhibiting inflammatory proteins
A new study led by researchers at the Massachusetts Comprehensive Cancer Center, a founding member of the Massachusetts Comprehensive Brigham Health System, has found that statins, a commonly used cholesterol-lowering drug, may inhibit a specific pathway involved in the development of cancers that result from chronic inflammation. Nature Communications.
“Chronic inflammation is a leading cause of cancer worldwide,” said senior author of the paper, Shawn Demery, MD, principal investigator in the Center for Cancer Immunology and Skin Biology Research at Massachusetts General Hospital and associate professor of dermatology at Harvard Medical School. “We investigated the mechanisms by which environmental toxins drive cancer-prone chronic inflammation in the skin and pancreas,” said Demery, who is also the 2023-2028 Bob and Rita Davis Family MGH Investigator. “Furthermore, we investigated safe and effective therapeutics to block this pathway to reduce chronic inflammation and its cancer sequelae.”
Demery and his colleagues' research relied on cell lines, animal models, human tissue samples, and epidemiological data. The group's cell-based experiments demonstrated that environmental toxins (such as exposure to allergens or chemical irritants) activate two related signaling pathways, called the TLR3/4 pathway and the TBK1-IRF3 pathway. This activation produces the interleukin-33 (IL-33) protein, which stimulates inflammation in the skin and pancreas and may lead to the development of cancer.
By screening a library of U.S. Food and Drug Administration-approved drugs, the researchers found that pitavastatin, a type of statin, effectively suppressed IL-33 expression by inhibiting the activation of the TBK1-IRF3 signaling pathway. In mice, pitavastatin suppressed environmentally induced inflammation in the skin and pancreas and prevented the development of inflammation-associated pancreatic cancer.
In human pancreatic tissue samples, IL-33 was overexpressed in samples from patients with chronic pancreatitis (inflammation) and pancreatic cancer compared to normal pancreatic tissue, and an analysis of electronic health record data from over 200 million people in North America and Europe showed that the use of pitavastatin significantly reduced the risk of chronic pancreatitis and pancreatic cancer.
The findings indicate that inhibition of IL-33 production by pitavastatin may be a safe and effective preventive strategy to suppress chronic inflammation and the subsequent development of certain cancers.
“Next, we aim to further explore the impact of statins in preventing the development of cancer in chronic inflammation of the liver and digestive tract, and to identify other novel therapeutic approaches to suppress chronic inflammation that predisposes to cancer,” Demery said.
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Sources 2/ https://www.sciencedaily.com/releases/2024/05/240530132346.htm The mention sources can contact us to remove/changing this article |
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