Lipids as Targets for Renal Cell Carcinoma Therapy

Int J Mol Sci. 2023 Feb 7;24(4):3272. doi: 10.3390/ijms24043272.

Abstract

Kidney cancer is among the top ten most common cancers to date. Within the kidney, renal cell carcinoma (RCC) is the most common solid lesion occurring. While various risk factors are suspected, including unhealthy lifestyle, age, and ethnicity, genetic mutations seem to be a key risk factor. In particular, mutations in the von Hippel-Lindau gene (Vhl) have attracted a lot of interest since this gene regulates the hypoxia inducible transcription factors HIF-1α and HIF-2α, which in turn drive the transcription of many genes that are important for renal cancer growth and progression, including genes involved in lipid metabolism and signaling. Recent data suggest that HIF-1/2 are themselves regulated by bioactive lipids which make the connection between lipids and renal cancer obvious. This review will summarize the effects and contributions of the different classes of bioactive lipids, including sphingolipids, glycosphingolipids, eicosanoids, free fatty acids, cannabinoids, and cholesterol to renal carcinoma progression. Novel pharmacological strategies interfering with lipid signaling to treat renal cancer will be highlighted.

Keywords: cannabinoids; cholesterol; eicosanoids; free fatty acids; glycosphingolipids; kidney cancer; lipids; renal cell carcinoma; sphingolipids.

Publication types

  • Review

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Carcinoma, Renal Cell* / drug therapy
  • Carcinoma, Renal Cell* / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / metabolism
  • Lipids
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Lipids
  • Von Hippel-Lindau Tumor Suppressor Protein

Grants and funding

This research received no external funding.