Statins role in cancer prevention and development-recent meta-analyses

Abstract

The therapeutic indications of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) include hypercholesterolaemia and the prevention of cardiovascular events. Statins are well tolerated and beyond their unambiguous positive cardiovascular effects there are a steadily increasing number of pleiotropic actions emerging. In this regard, growth inhibition, apoptosis, anti-inflammatory and immunomodulatory actions have been attributed to statins. The anti-proliferative effects have been the basis for massive preclinical investigations to elucidate a functional role for statins in carcinogenesis and tumor cell growth. However, preclinical and clinical studies are conflicting, although there is accumulating evidence that statins are capable to suppress and decrease the incidence and recurrence of some human cancers. Given the fact that statins are well tolerated they might also have some impact in combinations with conventional and targeted chemotherapy. While synergism has been shown for many combinations in vitro this does not hold true yet in the clinics. Here we review the rational behind usage of statins in oncological settings. Positive effects have been observed in patients with melanoma and cancers from the breast, colon, prostate, lung, liver and hematologic tissues. However, substantial evidence from clinical studies is still weak and confounded by several factors, which are inherent in the study design. The majority of the studies are observational or of retrospective nature. Definitely, there is substantial need for larger, prospective randomized, placebo-controlled trials. Finally, we conclude that statins at the current status of evidence should not be recommended in the prevention or during progression of any cancers, however, individual statins may have beneficial effects in specific tumor subgroups.

Keywords: 3-Hydroxy-3-methylglutaryl-coenzyme A-reductase inhibitors; Low density lipoprotein cholesterol; Cancer; Breast cancer; Apoptosis; Statins

Core tip: The 3-hydroxy-3 methyl CoA (HMG-CoA) reductase inhibitors, the statins are one of the most frequently prescribed drugs in industrialized countries. Statins are well tolerated cholesterol lowering drugs which significantly help to reduce cardiovascular events. Clinical trials and meta-analyzes thereof now accumulate evidence that development of cancer might be reduced in some tissues. In this review the current status of evidence for an anti-cancer effect of statins will be critically evaluated. In particular, colon and prostate cancer are assessed in greater detail.