Effects of statins and farnesyltransferase inhibitors on the development and progression of cancer

摘要: Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors - HMG-CoA inhibitors) have been approved for the treatment of lipid disorders. Recently, in vivo studies with experimental animals and vitro indicated a possible role statins malignancies. Inhibition enzyme results decreased farnesylation geranylgeranylation several proteins essential cellular proliferation survival. Ras was originally thought to be mechanism that mediates statin-induced effects cancer. Consequently, specific farnesyltransferase (FTIs) were developed. Currently, mechanisms mediate statin- FTI-induced antitumour are questioned. It remains unclear which signal transduction cascades involved. This review focuses on therapeutic application FTIs. Antitumour properties such as induction growth arrest apoptosis, inhibition metastasis angiogenesis discussed. Furthermore, inhibitor-induced involvement number components (such farnesylated geranylgeranylated proteins, mitogen-activated protein kinase signalling pathway, phosphoinositide 3'-kinase cell cycle regulatory proteins) reviewed. In addition, clinical epidemiological data respect summarised. We propose mevalonate pathway particularly effective when administered combination other drugs. Therefore, combined therapy or chemotherapeutics, biphosphonates, non-steroidal anti-inflammatory drugs, geranylgeranyltransferase tyrosine activity