Targeting dysregulated lipid metabolism in the tumor microenvironment

Arch Pharm Res. 2023 Dec;46(11-12):855-881. doi: 10.1007/s12272-023-01473-y. Epub 2023 Dec 7.

Abstract

The reprogramming of lipid metabolism and its association with oncogenic signaling pathways within the tumor microenvironment (TME) have emerged as significant hallmarks of cancer. Lipid metabolism is defined as a complex set of molecular processes including lipid uptake, synthesis, transport, and degradation. The dysregulation of lipid metabolism is affected by enzymes and signaling molecules directly or indirectly involved in the lipid metabolic process. Regulation of lipid metabolizing enzymes has been shown to modulate cancer development and to avoid resistance to anticancer drugs in tumors and the TME. Because of this, understanding the metabolic reprogramming associated with oncogenic progression is important to develop strategies for cancer treatment. Recent advances provide insight into fundamental mechanisms and the connections between altered lipid metabolism and tumorigenesis. In this review, we explore alterations to lipid metabolism and the pivotal factors driving lipid metabolic reprogramming, which exacerbate cancer progression. We also shed light on the latest insights and current therapeutic approaches based on small molecular inhibitors and phytochemicals targeting lipid metabolism for cancer treatment. Further investigations are worthwhile to fully understand the underlying mechanisms and the correlation between altered lipid metabolism and carcinogenesis.

Keywords: Cholesterol transport; Lipid uptake; Lipogenesis; Lipolysis; Phytochemical; Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Carcinogenesis
  • Humans
  • Lipid Metabolism
  • Lipids
  • Neoplasms* / pathology
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents
  • Lipids