Breakthrough in understanding how breast cancer spreads to the brain

Breast cancer is the most common cancer in women and can spread to distant organs, including the bones, lungs, liver, and brain. Among these, brain metastases (BM) are particularly devastating, as they are both among the deadliest and the most difficult to treat.

The TP53 gene, which encodes the p53 protein, is often inactivated in breast cancer cases. A large-scale international study investigated the role of p53 in the development of breast cancer BM (BCBM). The study involved the laboratories of Prof. Uri Ben-David and Prof. Ronit Satchi-Fainaro, in collaboration with dozens of researchers from 14 laboratories across six countries: Israel, the United States, Italy, Germany, Poland, and Australia. The study was published in Nature Genetics.

The researchers discovered that p53 inactivation markedly increased BCBM formation and growth in vivo, causally linking p53 perturbation to BM. Furthermore, p53 inactivation upregulated the enzyme SCD1 and fatty acid synthesis (FAS). The study also revealed a role for astrocytes, support cells that normally help brain neurons function. Astrocytes enhanced FAS by secreting factors that were metabolized in a p53-dependent manner, effectively helping metastatic cells establish themselves in the brain. These findings could pave the way for new therapies, as well as personalized monitoring strategies for the early detection and treatment of brain metastases.

Read the full paper:

p53 inactivation drives breast cancer metastasis to the brain through SCD1 upregulation and increased fatty acid metabolism

Published in: Nature Genetics

Authors: Kathrin Laue, Sabina Pozzi, Johanna Zerbib, Rebecca Bertolio, Yonatan Eliezer, Yael Cohen-Sharir, Tom Winkler, Manuel Caputo, Alessia A. Ricci, Lital Adler, Rami Khoury, Giuseppe Longobardi, Rachel Slutsky, Alicia I. Leikin-Frenkel, Shai Ovadia, Katharina Lange, Alessandra Rustighi, Silvano Piazza, Andrea Sacconi, Rayna Y. Magesh, Faith N. Keller, Jean Berthelet, Alexander Schäffer, Ron Saad, Sahar Israeli Dangoor, Karolina Szczepanowska, Iris Barshack, Yang Liao, Sergey Malitsky, Alexander Brandis, Thomas Broggini, Marcus Czabanka, Wei Shi, Delphine Merino, Emma V. Watson, Giovanni Blandino, Ayelet Erez, Ruth Ashery-Padan, Hind Medyouf, Luca Bertero, Giannino Del Sal, Ronit Satchi-Fainaro & Uri Ben-David

https://www.nature.com/articles/s41588-025-02446-1