A groundbreaking new study led by researchers from Mass General Cancer Center has uncovered a potential game-changer in the fight against cancer. The study, published in Nature Communications, reveals that statins, a commonly used class of cholesterol-lowering drugs, may hold the key to blocking a specific pathway involved in cancer development triggered by chronic inflammation.
Senior author Dr. Shawn Demehri, a leading researcher at the Center for Cancer Immunology and Cutaneous Biology Research Center of Massachusetts General Hospital, emphasized the significant impact of chronic inflammation on cancer worldwide. “We delved into the mechanism through which environmental toxins drive the onset of cancer-inducing chronic inflammation in the skin and pancreas,” stated Dr. Demehri, who is also the Bob and Rita Davis Family MGH Research Scholar 2023-2028. “Furthermore, we explored safe and effective therapies to disrupt this pathway and inhibit chronic inflammation and its cancerous implications.”
The research team’s comprehensive study utilized a range of tools, including cell lines, animal models, human tissue samples, and epidemiological data. Through cell-based experiments, they discovered that environmental toxins, such as allergens and chemical irritants, activate interconnected signaling pathways known as the TLR3/4 and TBK1-IRF3 pathways. This activation triggers the production of the interleukin-33 (IL-33) protein, initiating inflammation in the skin and pancreas that can pave the way for cancer development.
Interestingly, when screening a library of FDA-approved drugs, the researchers identified that pitavastatin, a type of statin, effectively suppresses IL-33 expression by inhibiting the activation of the TBK1-IRF3 signaling pathway. In animal models, pitavastatin successfully halted environmentally-induced inflammation in the skin and pancreas, ultimately preventing the emergence of inflammation-related pancreatic cancers.
In analyses of human pancreas tissue samples, the team observed an over-expression of IL-33 in samples from patients with chronic pancreatitis and pancreatic cancer compared to normal pancreatic tissue. Additionally, a review of electronic health records from over 200 million individuals across North America and Europe revealed a significant decrease in the risk of chronic pancreatitis and pancreatic cancer associated with the use of pitavastatin.
These findings highlight the potential of using pitavastatin to block IL-33 production as a safe and effective strategy to combat chronic inflammation and the subsequent development of specific cancers. “Our next steps involve delving deeper into the role of statins in preventing cancer in chronic inflammation of the liver and gastrointestinal tract, while also exploring novel therapeutic approaches to suppress cancer-prone chronic inflammation,” noted Dr. Demehri.
