Unraveling the Anticancer Potential of Statins: Mechanisms and Clinical Significance

SIMPLE SUMMARY: Statins are crucial for managing lipid disorders by inhibiting HMG-CoA reductase, reducing cholesterol levels, and lowering cardiovascular disease risk. Beyond cholesterol control, they exhibit pleiotropic effects, particularly in cancer. Statins influence key cancer pathways, inhibiting proliferation, angiogenesis, metastasis, and cancer stemness, while inducing oxidative stress, cell cycle arrest, autophagy, and apoptosis. Clinical studies suggest statin use associates with reduced cancer risk, lower-grade tumors at diagnosis, decreased local recurrence, and improved survival. This review aims to summarize the mechanisms underpinning statins’ anticancer properties and their clinical implications, highlighting their potential as a valuable tool in cancer prevention and treatment. ABSTRACT: Statins are an essential medication class in the treatment of lipid diseases because they inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. They reduce cholesterol levels and reduce the risk of cardiovascular disease in both primary and secondary prevention. In addition to their powerful pharmacologic suppression of cholesterol production, statins appear to have pleitropic effects in a wide variety of other diseases by modulating signaling pathways. In recent years, statins have seen a large increase in interest due to their putative anticancer effects. Statins appear to cause upregulation or inhibition in key pathways involved in cancer such as inhibition of proliferation, angiogenesis, and metastasis as well as reducing cancer stemness. Further, statins have been found to induce oxidative stress, cell cycle arrest, autophagy, and apoptosis of cancer cells. Interestingly, clinical studies have shown that statin use is associated with a decreased risk of cancer formation, lower cancer grade at diagnosis, reduction in the risk of local reoccurrence, and increasing survival in patients. Therefore, our objective in the present review is to summarize the findings of the publications on the underlying mechanisms of statins’ anticancer effects and their clinical implications.