Endogenous fat synthesis: a new therapeutic target against brain metastases in breast cancer

9 June 2022

Brain metastases are a very frequent cause of mortality in breast cancer patients. The incidence of this type of metastasis is between 10 and 15%, but this percentage reaches 50% in patients with the HER2+ breast cancer subtype. A new study led by ICO-IDIBGI in collaboration with the Mayo Clinic in the United States reviews the available clinical-molecular evidence to propose endogenous fat synthesis as a new therapeutic target against brain metastases in HER2+ breast cancer. The study is published in the latest issue of Expert Opinion on Therapeutic Targets, a journal specialized in offering expert opinion on the scope of new molecular targets in drug development and their impact on new drug discovery.

Dr. Javier A. Menendez, head of the "Metabolism and Cancer" group of the ProCURE Program at the Catalan Institute of Oncology-IDIBGI, and Dr. Ruth Lupu, from the Division of Experimental Pathology at the Mayo Clinic in Rochester (Minnesota, USA), highlight the ability of endogenous fatty acid synthesis catalyzed by the enzyme fatty acid synthase (FASN) to act as a "metabolic engine" that allows a certain group of cancer cells in the primary tumor to adapt, survive and "reproduce" in the fat-poor microenvironment characteristic of the brain. The paper by Drs. Menendez and Lupu provides a critical review of the opportunities and challenges offered by these discoveries.

The lipid-poor brain environment selects for breast cancer cells that are capable of autonomously synthesizing fatty acids.
Increased de novo lipid biosynthesis via FASN enables breast cancer cells to form metastatic brain lesions.
Selective disruption of the lipogenic program would prevent breast cancer cells from surviving in the brain microenvironment.
The development of FASN inhibitors capable of crossing the blood-brain barrier could provide a new therapeutic opportunity for the treatment and secondary prevention of breast cancer brain metastasis.

The "Metabolism and Cancer" group of the ICO-IDIBGI (https://idibgi.org/en/grups/metabolisme-i-cancer/) is currently working on the pre-clinical development of FASN inhibition for its forthcoming incorporation into the therapeutic armamentarium against brain metastasis in HER2+ breast cancer.