Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells

摘要: Statins, routinely used to treat hypercholesterolemia, selectively induce apoptosis in some tumor cells by inhibiting the mevalonate pathway. Recent clinical studies suggest that a subset of breast tumors is particularly susceptible lipophilic statins, such as fluvastatin. To quickly advance statins effective anticancer agents for cancer treatment, it critical identify molecular features defining this sensitive subset. We have therefore characterized fluvastatin sensitivity MTT assay panel 19 cell lines reflect diversity cancer, and evaluated association with several clinicopathological features. A wide range was observed across lines, triggering death lines. Fluvastatin associated an estrogen receptor alpha (ERα)-negative, basal-like subtype, can be scored routine and/or strong preclinical diagnostics. ascertain additional candidate sensitivity-associated features, we mined publicly available gene expression datasets, identifying genes encoding regulators production, non-sterol lipid homeostasis, global cellular metabolism, including oncogene MYC. Further exploration data allowed us generate 10-gene mRNA abundance signature predictive sensitivity, which showed preliminary validation independent set Here, identified predictors treatment warrant further evaluation.