NEW YORK, June 2: A recent study conducted by researchers at Mass General Cancer Center has shed light on the potential of statins, commonly used to lower cholesterol, in inhibiting a specific cancer-related pathway associated with chronic inflammation. Published in Nature Communications, the findings suggest promising implications for cancer prevention strategies.
Senior author Shawn Demehri, MD, PhD, a principal investigator at the Center for Cancer Immunology and Cutaneous Biology Research Center of Massachusetts General Hospital, highlighted the significance of chronic inflammation as a key contributor to cancer development globally. The study delved into the mechanisms through which environmental toxins trigger cancer-prone chronic inflammation in the skin and pancreas.
Utilizing a combination of cell lines, animal models, human tissue samples, and epidemiological data, Demehri and his team identified that environmental toxins activate interconnected signaling pathways known as the TLR3/4 and TBK1-IRF3 pathways, leading to the production of the interleukin-33 (IL-33) protein. IL-33, in turn, fuels inflammation in the skin and pancreas, fostering conditions conducive to cancer onset.
The researchers screened a library of U.S. Food and Drug Administration–approved drugs and found that a statin called pitavastatin effectively suppressed IL-33 expression by blocking the activation of the TBK1-IRF3 signaling pathway. In mouse models, pitavastatin demonstrated the ability to mitigate environmentally-induced inflammation in the skin and pancreas, thereby thwarting the development of inflammation-associated pancreatic cancers.
Analysis of human pancreas tissue samples revealed overexpression of IL-33 in patients with chronic pancreatitis and pancreatic cancer compared to normal pancreatic tissue. Moreover, examination of electronic health records data from over 200 million individuals across North America and Europe showed a significant reduction in the risk of chronic pancreatitis and pancreatic cancer associated with the use of pitavastatin.
These findings underscore the potential of pitavastatin in preventing cancer development by targeting IL-33 production and suppressing chronic inflammation. Moving forward, the researchers aim to explore the impact of statins in preventing cancer development in chronic inflammation affecting the liver and gastrointestinal tract, while also investigating novel therapeutic approaches to combat cancer-prone chronic inflammation.
The study received research support from various organizations, including the Burroughs Wellcome Fund, the LEO Foundation, the Sidney Kimmel Foundation, and the National Institutes of Health.