Statins [(3-hydroxy-3-methylglutaryl-coenzyme A reductase, HMG-CoA reductase, abbreviated HMGCR) inhibitors] inhibit cholesterol synthesis and are commonly used in the treatment and prevention of cardiovascular diseas...Statins [(3-hydroxy-3-methylglutaryl-coenzyme A reductase, HMG-CoA reductase, abbreviated HMGCR) inhibitors] inhibit cholesterol synthesis and are commonly used in the treatment and prevention of cardiovascular diseases. Preclinical and clinical studies have shown that the drug can be effective in several cancers including breast cancer which is the second most frequent cancer in the world and the commonest one among women. In breast cancer cell lines statins reduce proliferation, increase apoptosis, decrease invasion and sensitize them to radiation. Clinical trials in breast cancer patients have shown positive outcome in terms of decreased recurrence rate, decreased mortality and positive role as neoadjuvant agent. They may have a particular role in treatment-resistant cases like triple-negative or inflammatory breast cancer which have a poorer prognosis. There is also evidence of their potential use in metastatic bone disease from breast cancer. When statins inhibit 3-hydroxy-3-methylgutaryl CoA reductase which is the rate-limiting enzyme of the mevalonate pathway, the levels of mevalonate as well as its downstream products are decreased. Hence cancer growth is inhibited by reduced prenylation of CAAX proteins, N-Glycosylation of growth factor receptors and synthesis of membrane and steroid among others. Also statins are relatively cheap and can contribute to decrease the high cost of cancer treatment. However studies till now have not shown any association with decreased breast cancer incidence. In addition there are doubts regarding safety of statins when used over a prolonged period of time. Although statins are relatively safe with myotoxicity and hepatotoxicity being their major side effects, evidence regarding issues like drug interactions with anti-cancer drugs is lacking.展开更多
文摘Statins [(3-hydroxy-3-methylglutaryl-coenzyme A reductase, HMG-CoA reductase, abbreviated HMGCR) inhibitors] inhibit cholesterol synthesis and are commonly used in the treatment and prevention of cardiovascular diseases. Preclinical and clinical studies have shown that the drug can be effective in several cancers including breast cancer which is the second most frequent cancer in the world and the commonest one among women. In breast cancer cell lines statins reduce proliferation, increase apoptosis, decrease invasion and sensitize them to radiation. Clinical trials in breast cancer patients have shown positive outcome in terms of decreased recurrence rate, decreased mortality and positive role as neoadjuvant agent. They may have a particular role in treatment-resistant cases like triple-negative or inflammatory breast cancer which have a poorer prognosis. There is also evidence of their potential use in metastatic bone disease from breast cancer. When statins inhibit 3-hydroxy-3-methylgutaryl CoA reductase which is the rate-limiting enzyme of the mevalonate pathway, the levels of mevalonate as well as its downstream products are decreased. Hence cancer growth is inhibited by reduced prenylation of CAAX proteins, N-Glycosylation of growth factor receptors and synthesis of membrane and steroid among others. Also statins are relatively cheap and can contribute to decrease the high cost of cancer treatment. However studies till now have not shown any association with decreased breast cancer incidence. In addition there are doubts regarding safety of statins when used over a prolonged period of time. Although statins are relatively safe with myotoxicity and hepatotoxicity being their major side effects, evidence regarding issues like drug interactions with anti-cancer drugs is lacking.
