A recent study from the Mass General Cancer Center finds that statins may block a pathway involved in cancer development due to chronic inflammation, showing promise in preventing cancers associated with environmental toxins, particularly in skin and pancreas.
Research results show that pitavastatin suppresses skin and pancreatic cancers by inhibiting interleukin-33.
A recent study by researchers at the Mass General Cancer Center found that statins, widely used to lower cholesterol, may inhibit a specific pathway linked to the development of cancer caused by chronic inflammation. These results were reported in Natural communications.
“Chronic inflammation is a leading cause of cancer worldwide,” said lead author Shawn Demehri, MD, PhD, principal investigator at the Center for Cancer Immunology and Cutaneous Biology Research Center at Massachusetts General Hospital and associate professor of dermatology. at Harvard Medical School. . “We studied the mechanism by which environmental toxins lead to the initiation of chronic inflammation in cancer-prone skin and pancreas,” says Demehri, who is also a 2023-2028 Bob and Rita Davis Family MGH Research Fellow . “In addition, we examined safe and effective therapies to block this pathway to suppress chronic inflammation and its cancerous consequences. »
Research methods and results
Demehri and colleagues’ study relied on cell lines, animal models, human tissue samples and epidemiological data. The group’s cellular experiments demonstrated that environmental toxins (such as exposure to allergens and chemical irritants) activate two connected signaling pathways called the TLR3/4 and TBK1-IRF3 pathways. This activation leads to the production of the protein interleukin-33 (IL-33), which stimulates inflammation in the skin and pancreas that can contribute to the development of cancer.
When they screened a library of drugs approved by the U.S. Food and Drug Administration, researchers found that a statin, pitavastatin, effectively suppresses the expression of IL-33 by blocking the activation of the TBK1-IRF3 signaling pathway. In mice, pitavastatin suppressed environmentally induced inflammation of the skin and pancreas and prevented the development of inflammation-related pancreatic cancers.
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. Additionally, in analyzes of electronic health record data from more than 200 million people in North America and Europe, pitavastatin use was associated with a significantly reduced risk of chronic pancreatitis and pancreatic cancer. .
The results demonstrate that blocking IL-33 production with pitavastatin may provide a safe and effective preventative strategy to suppress chronic inflammation and the subsequent development of certain cancers.
“Next, we aim to further examine the impact of statins in preventing cancer development in chronic inflammation of the liver and gastrointestinal tract and identify other novel therapeutic approaches to suppress inflammation chronically cancer-prone,” Demehri said.
Reference: “Statin prevents cancer development in chronic inflammation by blocking interleukin 33 expression” by Jong Ho Park, Mahsa Mortaja, Heehwa G. Son, Xutu Zhao, Lauren M. Sloat, Marjan Azin, Jun Wang, Michael R. Collier, Krishna S. . Tummala, Anna Mandinova, Nabeel Bardeesy, Yevgeniy R. Semenov, Mari Mino-Kenudson and Shadmehr Demehri, May 30, 2024, Natural communications.
DOI: 10.1038/s41467-024-48441-8
Research support was provided by the Burroughs Wellcome Fund, the LEO Foundation, the Sidney Kimmel Foundation and the National Institutes of Health.
News Source : scitechdaily.com
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