Targeting lipid metabolism in the treatment of ovarian cancer

Oncotarget. 2022 May 25:13:768-783. doi: 10.18632/oncotarget.28241. eCollection 2022.

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.

Keywords: biomarkers; fatty acid; lipid metabolism; microenvironment; ovarian cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetyl-CoA Carboxylase / metabolism
  • Adenosine Triphosphate / metabolism
  • Carcinogenesis
  • Carcinoma, Ovarian Epithelial
  • Fatty Acid Synthases / metabolism
  • Fatty Acid-Binding Proteins / metabolism
  • Fatty Acids / metabolism
  • Fatty Acids, Unsaturated
  • Female
  • Humans
  • Lipid Metabolism* / physiology
  • Lipogenesis
  • Lipoproteins, LDL / metabolism
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / pathology
  • Stearoyl-CoA Desaturase / metabolism

Substances

  • Fatty Acid-Binding Proteins
  • Fatty Acids
  • Fatty Acids, Unsaturated
  • Lipoproteins, LDL
  • Adenosine Triphosphate
  • Stearoyl-CoA Desaturase
  • Fatty Acid Synthases
  • Acetyl-CoA Carboxylase