The therapeutic indications of 3-hydroxy-3-methylgl-utaryl-coenzyme A （HMG-CoA） reductase inhibitors （statins） include hypercholesterolaemia and the pre-vention of cardiovascular events. Statins are well toler-ate...The therapeutic indications of 3-hydroxy-3-methylgl-utaryl-coenzyme A （HMG-CoA） reductase inhibitors （statins） include hypercholesterolaemia and the pre-vention of cardiovascular events. Statins are well toler-ated and beyond their unambiguous positive cardio-vascular effects there are a steadily increasing number of pleiotropic actions emerging. In this regard, growth inhibition, apoptosis, anti-infammatory and immuno-modulatory actions have been attributed to statins. The anti-proliferative effects have been the basis for massive preclinical investigations to elucidate a func-tional 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. Giv-en the fact that statins are well tolerated they might also have some impact in combinations with conven-tional 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 set-tings. 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 ob-servational or of retrospective nature. Defnitely, 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 benefcial effects in specifc tumor subgroups.展开更多
基金Supported by The Herzfeldersche Familienstiftung and the Austrian Science foundation,FWF-Project P22385
文摘The therapeutic indications of 3-hydroxy-3-methylgl-utaryl-coenzyme A （HMG-CoA） reductase inhibitors （statins） include hypercholesterolaemia and the pre-vention of cardiovascular events. Statins are well toler-ated and beyond their unambiguous positive cardio-vascular effects there are a steadily increasing number of pleiotropic actions emerging. In this regard, growth inhibition, apoptosis, anti-infammatory and immuno-modulatory actions have been attributed to statins. The anti-proliferative effects have been the basis for massive preclinical investigations to elucidate a func-tional 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. Giv-en the fact that statins are well tolerated they might also have some impact in combinations with conven-tional 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 set-tings. 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 ob-servational or of retrospective nature. Defnitely, 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 benefcial effects in specifc tumor subgroups.
