Therapy insight: Potential of statins for cancer chemoprevention and therapy.

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are commonly prescribed medications that lower serum cholesterol and decrease cardiac morbidity and mortality. These agents inhibit the rate-limiting step of the mevalonate pathway, an effect that influences cholesterol homeostasis and other diverse cellular functions. Preclinical data suggest statins have pleiotropic antineoplastic effects in a variety of tumors, but clinical studies have provided conflicting data regarding whether statins may increase or decrease the risk of cancer. Abnormal cholesterol metabolism in cancer is poorly understood but should be considered when evaluating the antineoplastic effects of statins. Emerging evidence suggests that atherosclerosis and cancer have similar underlying molecular mechanisms, both having lipid abnormalities and a pro-inflammatory phenotype. Like nonsteroidal anti-inflammatory agents, statins target lipid metabolism, have significant anti-inflammatory effects, and can influence cardiovascular mortality. Recent studies show that statins may have chemopreventive effects and may complement cytotoxic chemotherapy or radiotherapy as a biologic response modifier in established cancer, but current data do not support their use as monotherapy. The preclinical data supporting anticancer activity, their additional health benefits, and the safety and relative low cost of statins compared to other 'targeted' agents currently under development all favor conducting prospective clinical trials of these drugs in cancer chemoprevention and therapy.