hero image

Chronic inflammation is a significant factor in cancer development, accounting for around 20% of cases. Researchers have identified a molecular pathway connecting inflammation and cancer and found that statins, a type of cholesterol-lowering medication, can disrupt this link.

Statins could help treat cancer

The recent study in Nature Communications by researchers from Massachusetts General Hospital and Harvard Medical School investigated interleukin-33 (IL-33), a protein released by damaged cells to signal the immune system. While IL-33 normally prompts beneficial inflammation to fight infection or aid healing, persistent high levels in chronic inflammation promote tumor growth.

Scientists have discovered a connection between statins and cancer development. They found that the production of IL-33, a protein associated with cancer, is triggered by a signaling pathway involving toll-like receptors (TLRs), TBK1, and IRF3 proteins. TLRs detect molecular patterns linked to pathogens or cell damage, activating a cascade that leads to the activation of IRF3 and the subsequent expression of the IL-33 gene.

Researchers found that pitavastatin, a statin drug, disrupts inflammatory processes. Statins are commonly used to reduce cholesterol and heart disease risk by inhibiting HMG-CoA reductase, a key enzyme in cholesterol synthesis.

Pitavastatin, a type of statin medication, decreases levels of geranylgeranyl diphosphate (GGPP), a crucial molecule. GGPP is necessary for activating TBK1, a vital part of inflammatory signaling. Lower GGPP levels due to pitavastatin lead to reduced TBK1 activation, consequently inhibiting IL-33 production.

Pitavastatin reduces inflammation and IL-33 levels

Interestingly, pitavastatin treatment showed significant reduction in inflammation and IL-33 levels in mouse models of inflammatory skin conditions and pancreatitis, a risk factor for pancreatic cancer. Additionally, in mice engineered to develop pancreatic cancer, pitavastatin slowed tumor progression and prolonged survival.

The study highlighted the significance of IRF3 and IL-33 in pancreatic cancer through analysis of human samples. It was found that patients using pitavastatin had reduced risk of pancreatitis and pancreatic cancer compared to users of other cholesterol-lowering medications.

Dr. Shawn Demehri, a principal investigator, emphasizes the link between chronic inflammation and cancer, focusing on how environmental toxins contribute to this process in the skin and pancreas.