The lipid droplet in cancer: From being a tumor-supporting hallmark to clinical therapy

Acta Physiol (Oxf). 2024 Mar;240(3):e14087. doi: 10.1111/apha.14087. Epub 2024 Jan 22.

Abstract

Introduction: Abnormal lipid metabolism, one of the hallmarks in cancer, has gradually emerged as a novel target for cancer treatment. As organelles that store and release excess lipids, lipid droplets (LDs) resemble "gears" and facilitate cancer development in the body.

Aim: This review discusses the life cycle of LDs, the relationship between abnormal LDs and cancer hallmarks, and the application of LDs in theragnostic and clinical contexts to provide a contemporary understanding of the role of LDs in cancer.

Methods: A systematic literature search was conducted in PubMed and SPORTDiscus. Retrieve and summarize clinical trials of drugs that target proteins associated with LD formation using the Clinical Trials website. Create a schematic diagram of lipid droplets in the tumor microenvironment using Adobe Illustrator.

Conclusion: As one of the top ten hallmarks of cancer, abnormal lipid metabolism caused by excessive generation of LDs interrelates with other hallmarks. The crosstalk between excessive LDs and intracellular free fatty acids (FFAs) promotes an inflammatory environment that supports tumor growth. Moreover, LDs contribute to cancer metastasis and cell death resistance in vivo. Statins, as HMGCR inhibitors, are promising to be the pioneering commercially available anti-cancer drugs that target LD formation.

Keywords: cancer treatment; lipid droplet; lipid metabolism; metabolic enzymes.

Publication types

  • Review

MeSH terms

  • Cell Death
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Lipid Droplets
  • Lipid Metabolism
  • Neoplasms* / drug therapy
  • Tumor Microenvironment

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors