Lipids and breast cancer: metabolic reprogramming as a therapeutic target

#BreastCancer #LipidMetabolism #FASN #Ferroptosis #TumorMicroenvironment  


Breast cancer (BC) remains one of the most feared cancers, particularly among women aged 30 to 60. While therapeutic advances have improved survival rates, a harsh reality persists: some tumors resist treatment, recur, or metastasize. Why? A remarkable ability of tumor cells to reprogram their lipid metabolism. This is one of the key insights highlighted in a recent review published in Molecular Cancer.   

From lipid transporters to fatty acid synthesis and mitochondrial oxidation, cancer cells exploit lipids for energy, structure, and signaling. This reprogramming also reshapes the tumor microenvironment (TME), contributing to immune evasion and metastatic progression.

Lipids as fuel for malignancy

Breast cancer cells adapt their metabolism to absorb more fatty acids through receptors such as CD36, FABP4, or LDLR. Once inside the cell, these lipids are processed by key enzymes like FASN (fatty acid synthase), ACC, and SCD1—enzymes that are significantly overactive in aggressive and treatment-resistant tumors.

FASN has emerged as a potential biomarker for HER2-positive and triple-negative breast cancers, linked to tamoxifen resistance and metastatic progression. As for cholesterol, enzymes such as HMGCR and SQLE, when highly activated, promote the formation of lipid rafts that favor the activation of growth receptors like EGFR and HER2.  

Read next: HER2, the key to revolutionizing cancer treatment

Lipid oxidation and ferroptosis: opposing pathways, one shared challenge

Fatty acid oxidation (FAO) allows tumor cells to survive metabolic stress, especially under chemotherapy. Enzymes like CPT1A and CPT2 are associated with tumor proliferation and migration. On the other hand, ferroptosis—a form of cell death triggered by lipid peroxidation—represents an exploitable metabolic vulnerability. Targets such as GPX4 and ACSL4 are now being explored in immunotherapy or in combination with CDK4/6 inhibitors.

Lipids also impact immune cells in the TME: macrophages, NK cells, T cells, and dendritic cells all show metabolic alterations that weaken their anti-tumor efficacy.  

Toward targeted lipid oncology?

Preclinical studies are already focusing on inhibitors of FASN (e.g., TVB-2640, orlistat), cholesterol synthesis (e.g., statins), FAO (e.g., etomoxir), and ferroptosis inducers.

The goal? To restore tumor sensitivity to conventional therapies while reshaping the TME into an immunocompetent environment.

In this context, lipid reprogramming is emerging as a new frontier in precision oncology. Integrating lipidomics and targeting lipid metabolic pathways in breast cancer could pave the way for more effective and durable combination strategies, especially for aggressive or treatment-resistant forms.  

Read next: Ferroptosis: activating iron to overcome treatment-resistant cancers?

About the Author – Lila Rouland
Doctor of Oncology, specialized in Biotechnology and Management

With dual expertise in science and marketing, Lila brings her knowledge to the service of healthcare innovation. After five years in international academic research, she transitioned into medical and scientific communication within the pharmaceutical industry. Now working as a medical writer and content developer, she is committed to highlighting scientific knowledge and conveying it to healthcare professionals with clarity and relevance.