摘要
Most breast cancers are hormone-receptor positive(HR+).However,more women eventually die from HR+breast cancer than from either HER2+or triple negative breast cancer.Endocrine therapies continue to be the mainstay of treatment.In 40%of these cases,recurrences in early-stage disease and progression in the metastatic setting are largely a function of the development of endocrine resistance.A multitude of mediators and pathways have been associated with endocrine resistance in breast cancer including the mevalonate pathway,which is integral to cholesterol biosynthesis.The mevalonate pathway and the downstream activation of associated cytoplasmic pathways including PI3K-AKT-mTOR and RAS-MEK-ERK have been known to affect cancer cell proliferation,cell survival,cell invasion,and metastasis.These are important mechanisms leading to the inevitable development of endocrine resistance in HR+breast cancer.Statins are a class of drugs that inhibits HMG-CoA reductase,an enzyme in the mevalonate pathway that plays a central role in cholesterol production.In vitro and in vitro studies suggest that the role of statins in blocking the mevalonate pathway effectively disrupts downstream pathways involved in estrogen receptor expression and cellular processes such as cell survival,proliferation,stress,cell cycle,inhibition of apoptosis,and autophagy.Overcoming these key mechanisms heralds a role for statins in the prevention of endocrine resistance.
