December 2025: Breakthrough discovery: Ben-David and colleagues identify mechanism behind breast cancer brain metastasis

A major international study, published in Nature Genetics, and led by Prof. Uri Ben‑David, Edmond J. Safra member, and Prof. Ronit Satchi‑Fainaro (Medical & Health Sciences), set out to answer a long‑standing question in cancer biology: What allows breast cancer cells to metastasize specifically to the brain, and why are these metastases so aggressive and hard to treat? To investigate this, TAU team collaborated with dozens of researchers from 14 laboratories in six countries (Israel, United States, Italy, Germany, Poland, and Australia).

The study combined two distinct approaches to cancer research based on the expertise of the two labs: Prof. Satchi-Fainaro’s lab, which studies the interactions between cancer cells and their surrounding environment (the tumor microenvironment), and Prof. Ben-David’s lab, which investigates chromosomal changes that characterize cancer cells. The complex study involved numerous scientific methods and technologies, including clinical and genomic data analysis of tumors from breast cancer patients, genetic, biochemical, metabolic, and pharmacological experiments in cultured cancer cells, and functional experiments in mice.

The researchers discovered that breast cancer cells destined for the brain often lose part of chromosome 17’s short arm, a region that contains the critical tumor‑suppressor gene p53. According to Prof. Ben‑David, the absence of functional p53 "dramatically increases the ability of cancer cells to survive and expand in the brain", because these cells adapt their metabolism in ways normal breast cancer cells cannot. The researchers found that this genetic change enables cancer cells to rewire how they make fatty acids, a metabolic process essential for survival in the brain’s unique environment. Prof. Satchi‑Fainaro explains that cells lacking p53 "produce far more fatty acids, giving them a growth advantage once they reach the brain". These cancer cells also interact more strongly with astrocytes, support cells in the brain, and exploit molecules secreted by these astrocytes to fuel their accelerated fatty‑acid production.

A key enzyme in this metabolic shift, SCD1, was found to be highly active in cancer cells missing p53. Once the team identified SCD1 as a central player, they tested drugs that inhibit this enzyme. These compounds, originally developed for other diseases, significantly reduced the growth of brain metastases in both mouse models and tissue samples from patients with breast‑cancer brain metastases. Prof. Ben‑David noted that blocking SCD1 "substantially impaired the metastatic cells’ ability to thrive in the brain".

These findings have important clinical implications. Because p53 loss (or deletion of the relevant chromosomal region) can be detected early in the disease, physicians may identify which patients are likely to develop brain metastases and tailor treatment and monitoring accordingly, avoiding unnecessary toxic therapies for low‑risk patients while providing intensive surveillance or early intervention for high‑risk individuals. By uncovering how breast cancer cells adapt to and exploit the brain environment, the study provides a mechanistic explanation for a lethal clinical problem and points to promising drug targets for conditions that currently lack effective treatment.

The study received wide media coverage: JNS, JPOST, JC, ISRAELECONOMICO, AJN, technologynetworks, medicalxpress, azertag, Miragenews, Xalqqazeti, ITONGADOL, JEWISHNEWS, JANGLO, infosalus, and more.