Christopher D. Lao, MD, MPH

Increasing epidemiologic data haveemerged to support an associationbetween 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductaseinhibitor (statin) use and theprevention or delay in the developmentof invasive cancer. The inhibitionof HMG-CoA reductase resultsin the depletion of mevalonate, a precursorof cholesterol, but also of geranylgeranylpyrophosphate andfarnesyl pyrophosphate, both ofwhich are critical for the isoprenylationof important cellular signalingproteins. Alterations in function andexpression of these signaling proteins-particularly Ras and Rho-have been implicated in malignanttransformation and proliferation. Furthermore,the epidemiologic data arebeing surpassed by preclinical datasupporting the concept that inhibitionof critical signaling pathways bystatins can lead to increased cell deathand prevent the proliferation of malignantcells.