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Targeting lipid metabolism enzymes in breast cancer: Mechanistic basis and therapeutic vulnerabilities

Xinpeng Li1, Hua Hao1

  • 1Department of Pathology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, PR China.

European Journal of Pharmacology
|July 9, 2026
PubMed

Insights

Lipid metabolism enzymes drive breast cancer progression and resistance. Targeting these enzymes offers therapeutic potential but faces challenges in toxicity and patient selection.

Area of Science:

  • Biochemistry
  • Oncology
  • Metabolomics

Background:

  • Breast cancer exhibits metabolic heterogeneity, with lipid metabolism enzymes playing key roles.
  • These enzymes influence tumor progression, microenvironment adaptation, and treatment response.
  • They link lipid metabolism to critical processes like membrane remodeling, drug resistance, and cell plasticity.

Purpose of the Study:

  • To review lipid metabolism enzymes as drivers of breast cancer phenotypes and treatment resistance.
  • To analyze subtype-specific roles and therapeutic vulnerabilities associated with these enzymes.
  • To examine current and emerging pharmacological strategies targeting lipid metabolism in breast cancer.

Main Methods:

  • Literature review adopting a subtype-aware, node-based framework.
  • Analysis of enzymes involved in fatty acid, cholesterol, and phospholipid metabolism.
  • Examination of pharmacological interventions targeting lipid metabolic pathways.

Main Results:

  • Lipid metabolism enzymes are context-dependent drivers of malignant phenotypes and multidrug resistance (MDR).
  • Targeting strategies include FASN inhibition, ferroptosis induction, fatty acid oxidation blockade, and cholesterol metabolism modulation.
  • Current strategies are mostly preclinical, facing challenges like toxicity, metabolic compensation, and heterogeneity.

Conclusions:

  • Lipid metabolism enzymes represent potential therapeutic vulnerabilities in breast cancer.
  • Further research requires mechanistic validation and biomarker-driven patient stratification.
  • Development of rational combination therapies is crucial for effective treatment.
Keywords:
Biomarker-guided therapyBreast cancerFerroptosisLipid metabolism enzymesMultidrug resistanceTherapeutic vulnerabilityTumor microenvironment

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