Abstract B22 : identification of novel drug combinations to target molecular pathways involved in breast cancer

Abstract

Introduction: At a global level breast cancer is the second most common cancer, and the most frequent in women. Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) inhibitors. HMG-CoA reductase is a rate-limiting enzyme in the mevalonate pathway, making it important in the pathology of cancer. The serine/threonine kinase, mammalian target of rapamycin (mTOR)regulates cell survival, proliferation and growth via translational initiation control, and this pathway is deregulated in many types of cancer which are associated with phosphatidylinositol-3-kinase (PI3K)/Akt signaling activation. HMG-CoA reductase expression is dependent oneukaryotic translation initiation factor 4E (eIF4E), and requires high translation initiation efficiency for polysome recruitment. eIF4E availability is reduced by mTOR inhibitors such asrapamycin and metformin, leading to a reduction in HMG-CoA reductase expression. [Excerpt]