A recent study at the Mass General Cancer Center showed that statins can block the pathways involved in cancer development by causing chronic inflammation, showing promise in protecting against environmental toxins, particularly cancers of the skin and pancreas.
Research findings show that pittastatin prevents 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 block a pathway linked to the development of cancer due to chronic inflammation. These results were recorded in Natural relationships.
“Chronic inflammation is a leading cause of cancer worldwide,” said senior author Shawn Demehri, MD, PhD, principal investigator of the Cancer Immunology and Skin Biology Research Center at Massachusetts General Hospital and associate professor of dermatology at Harvard Medical School. . “We investigated the mechanism by which environmental toxins induce cancer-prone chronic inflammation in the skin and pancreas,” said Demehri, a 2023-2028 Bob and Rita Davis Family MGH Research Scholar. “We have also investigated safe and effective therapies to block this pathway in order to prevent chronic inflammation and the consequences of cancer.”
Research methods and findings
Demehri and his colleagues’ research is based on cell lines, animal models, human tissue samples and epidemiological data. The team’s cell-based experiments show that environmental toxins (such as exposure to allergens and chemical irritants) activate two related signaling pathways called TLR3/4 and TBK1-IRF3. This activation leads to the production of interleukin-33 (IL-33), a protein that stimulates inflammation in the skin and pancreas, which contributes to the development of cancer.
Examining a library of US Food and Drug Administration-approved drugs, the researchers found that the statin pitastatin effectively inhibited IL-33 expression by blocking the TBK1-IRF3 signaling pathway. Pitastatin inhibits local inflammation in the skin and pancreas and prevents inflammation-related pancreatic cancers in mice.
In human pancreatic tissue samples, IL-33 was overexpressed in samples from patients with chronic pancreatitis and pancreatic cancer compared to normal pancreatic tissue. Also, in electronic health record data on more than 200 million people in North America and Europe, the use of pitavastatin significantly reduces the risk of developing chronic pancreatitis and pancreatic cancer.
The findings suggest that blocking IL-33 production with pitavastatin may be a safe and effective preventive strategy to prevent chronic inflammation and the subsequent development of certain cancers.
“Next, we aim to further investigate the effect of statins on the prevention of cancer progression in liver and gastrointestinal tract chronic inflammation and to identify other novel therapeutic strategies to inhibit cancer-prone chronic inflammation,” said Demehri.
Reference: “Statin Inhibits Cancer Growth in Chronic Inflammation by Inhibiting Interleukin 33 Expression” by Jung Ho Park, Mahsa Mortaja, Hehwa G Son, Shutu Zhao, Lauren M. Sloat, Marjan Azin, Jun Wang, Michael R. Collier, Krishna S.; Anna Mandinova, Nabel Bardesi, Yevgeny R. Semenov, Marie Mino-Kenudson, and Shadmehr Demehri, 30 May 2024; Natural relationships.
DOI: 10.1038/s41467-024-48441-8
Research support by the Burroughs Wellcome Fund, the Leo Foundation, the Sidney Kimmel Foundation, and National Institutes of Health.