Cholesterol and beyond - The role of the mevalonate pathway in cancer biology.

Andy Göbel, Martina Rauner, Lorenz C Hofbauer, Tilman D Rachner

Journal: Biochimica et biophysica acta. Reviews on cancer 2020;1873(2):188351

PMID: 32007596

Full Text on Elsevier Science View on PubMed

Abstract

Cancer is a multifaceted global disease. Transformation of a normal to a malignant cell takes several steps, including somatic mutations, epigenetic alterations, metabolic reprogramming and loss of cell growth control. Recently, the mevalonate pathway has emerged as a crucial regulator of tumor biology and a potential therapeutic target. This pathway controls cholesterol production and posttranslational modifications of Rho-GTPases, both of which are linked to several key steps of tumor progression. Inhibitors of the mevalonate pathway induce pleiotropic antitumor-effects in several human malignancies, identifying the pathway as an attractive candidate for novel therapies. In this review, we will provide an overview about the role and regulation of the mevalonate pathway in certain aspects of cancer initiation and progression and its potential for therapeutic intervention in oncology.

Address: Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: [email protected].; Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany.

DOI: 10.1016/j.bbcan.2020.188351

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MeSH Terms: Antineoplastic Agents, Cell Proliferation, Cell Transformation, Neoplastic, Cholesterol, Clinical Trials as Topic, Disease Progression, Geranyltranstransferase, Humans, Hydroxymethylglutaryl CoA Reductases, Metabolic Networks and Pathways, Mevalonic Acid, Neoplasms, Protein Processing, Post-Translational, Sterol Regulatory Element Binding Proteins, Treatment Outcome, rho GTP-Binding Proteins