The mevalonate pathway in breast cancer biology. (28th August 2022)

• Record Type: Journal Article
• Authors: Göbel, Andy; Riffel, Romy M.; Hofbauer, Lorenz C.; Rachner, Tilman D.
• Is Part Of: Cancer letters. Volume 542(2022)
• Publication Date: 2022-08-28
• Subjects: Breast cancer -- Statins -- Amino-bisphosphonates -- Cholesterol -- Rho-GTPases; 27-hydroxycholesterol (27-HC) -- 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) -- acetyl-coenzyme A (acetyl-CoA) -- adenosine triphosphate (ATP) -- amino-bisphosphonates (N-BP) -- aromatase inhibitors (AI) -- ATP citrate lyase (ACLY) -- breast cancer (BrCa) -- epithelial-to-mesenchymal transition (EMT) -- estrogen receptor (ER) -- farnesyl diphosphate synthase (FDPS) -- farnesyl pyrophosphate (FPP) -- geranylgeranyl pyrophosphate (GGPP) -- guanosine triphosphate (GTP) -- human epidermal growth factor receptor 2 (HER2) -- interferon γ (IFN-γ) -- low density lipoprotein (LDL) -- low density lipoprotein receptor (LDLR) -- mammalian target of rapamycin (mTOR) -- mitogen activated protein kinases (MAPK) -- matrix metalloproteinases (MMP) -- nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFκB) -- natural killer cells (NK cells) -- programmed death-ligand 1 (PD-L1) -- regulatory T Cells (Tregs) -- sterol regulatory element binding protein (SREBP) -- tumor-associated macrophages (TAM) -- tumor microenvironment (TME) -- triple-negative breast cancer (TNBC) -- Yes-associated protein (YAP) -- transcriptional co-activator with PDZ-binding motif (TAZ); Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2022.215761
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Breast cancer affects one in eight women during their lifetime. Although diagnostic and therapeutic options have improved, recurrence, metastasis, and therapeutic resistance remain clinical challenges, which affect life quality and prognosis. The mevalonate pathway is an essential part of cellular homeostasis by providing a number of essential isoprenoid products including cholesterol. However, the disturbance of this pathway paralleled by increased bioavailability of its products and their direct involvement in several steps of tumorigenesis has highlighted the mevalonate pathway as a promising hub in cancer treatment. In this review, we will specifically discuss how the mevalonate pathway affects breast cancer biology in terms of supporting and modulating soluble and cellular factors and distinct steps of tumorigenesis. We will further summarize antitumor effects of the mevalonate pathway-inhibiting drugs, statins and amino-bisphosphonates, in breast cancer and discuss how they are used for future precision therapy. Highlights: Dysregulated mevalonate pathway activity is associated with several steps of breast cancer tumorigenesis. Cholesterol and derivative oncometabolites drive tumor growth, metastasis, and therapeutic resistance in breast cancer. Statins and amino-bisphosphonates exert numerous anti-cancer effects in preclinical and clinical studies. Specific biomarkers and optimal treatment regimens are needed to precisely utilize these drugs in breast cancer therapy.