The Role of Statins in Cancer Therapy

Abstract

Learning ObjectivesAfter completing this course, the reader will be able to:1. Explain how statins, used in the treatment of hypercholesterolemia, may be applicable to cancer prevention.2. Discuss how statins potentially interfere with biologic processes relevant to cancer etiology. AbstractAdministration of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, to ambulatory patients is associated with a lower incidence of long-term adverse cardiovascular events, including death, myocardial infarction, stroke, atrial fibrillation, and renal dysfunction. However, increasing clinical evidence suggests that statins, independent of their effects on serum cholesterol levels, may also play a potential role in the prevention and treatment of cancer. Specifically, statins have been shown to exert several beneficial antineoplastic properties, including decreased tumor growth, angiogenesis, and metastasis. The feasibility and efficacy of statins for the prevention and treatment of cancer is reviewed. The Oncologist 2006;11:306-315

Phenotype-based high-content chemical library screening identifies statins as inhibitors of in vivo lymphangiogenesis

“…They reduce low-density lipoprotein (LDL) levels in the plasma by inhibiting the 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase (HMGCR) and thereby cholesterol synthesis (38). Recently, there has been increasing interest in their effects on cancer development (38). The hypothesis that statins might promote the risk for cancer development was not supported in the rosuvastatin/JUPITER trial (39).…”

Estrogen Receptor–Negative Breast Cancer Is Less Likely to Arise among Lipophilic Statin Users

“…Although epidemiologic evidence for statin use and cancer prevention remains controversial, preclinical evidence supporting the anticancer potential of lipophilic but not hydrophilic statins is quite strong, prompting numerous reviews and prominent calls for prospective clinical assessment of statins as cancer therapeutics and prevention agents (1,6,(19)(20)(21)(22). In vitro and in vivo treatment of cancer models by lipophilic statins invariably reduces intracellular levels of mevalonate and its downstream products, including the isoprenoid intermediates that provide lipid attachment sites for activated Ras, Rac, and Rho family members (23).…”

Effects of statins on the prognosis of local and locally advanced renal cell carcinoma following nephrectomy

“…Statins exert pro-apoptotic properties in a variety of tumor cells, by which they upregulate pro-apoptotic proteins, decrease anti-apoptotic proteins and activate certain types of caspases (19,20). Statins impair the metastatic potential of tumor cells by inhibiting cell migration, attachment to the extracellular matrix and invasion of basement membrane (21).…”