Targeting lipid metabolism in the treatment of ovarian cancer

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// Saliha Chaudhry 1 , Stefani N. Thomas 2 and Glenn E. Simmons Jr. 3 1 Department of Medicine, University of Minnesota School of Medicine, Twin Cities, MN 55455, USA 2 Department of Laboratory Medicine and Pathology, University of Minnesota School of Medicine, Twin Cities, MN 55455, USA 3 Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA Correspondence to: Glenn E. Simmons Jr., email: glenn.simmons@cornell.edu Keywords: ovarian cancer; lipid metabolism; biomarkers; microenvironment; fatty acid Received: July 05, 2021 Accepted: May 07, 2022 Published: May 25, 2022 Copyright: © 2022 Chaudhry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Cancer cells undergo alterations in lipid metabolism to support their high energy needs, tumorigenesis and evade an anti-tumor immune response. Alterations in fatty acid production are controlled by multiple enzymes, chiefly Acetyl CoA Carboxylase, ATP-Citrate Lyase, Fatty Acid Synthase, and Stearoyl CoA Desaturase 1. Ovarian cancer (OC) is a common gynecological malignancy with a high rate of aggressive carcinoma progression and drug resistance. The accumulation of unsaturated fatty acids in ovarian cancer supports cell growth, increased cancer cell migration, and worse patient outcomes. Ovarian cancer cells also expand their lipid stores via increased uptake of lipids using fatty acid translocases, fatty acid-binding proteins, and low-density lipoprotein receptors. Furthermore, increased lipogenesis and lipid uptake promote chemotherapy resistance and dampen the adaptive immune response needed to eliminate tumors. In this review, we discuss the role of lipid synthesis and metabolism in driving tumorigenesis and drug resistance in ovarian cancer conferring poor prognosis and outcomes in patients. We also cover some aspects of how lipids fuel ovarian cancer stem cells, and how these metabolic alterations in intracellular lipid content could potentially serve as biomarkers of ovarian cancer.

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