By Lila Rouland | Published on July 22, 2025 | 2 min read
#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.
