A late complication of breast cancer, brain metastases significantly reduce life expectancy of women suffering from the disease. Thanks to a new preclinical model, scientists at the University of Fribourg have identified one of the mechanisms involved in this often fatal development, as well as new therapeutic targets. Important results pointing to new treatments.

Breast cancer is the most frequent form of cancer among women, both in Switzerland and around the world. Over the past few decades, important therapeutic progress has been achieved in treating breast cancer, with not only an improvement in patients’ quality of life but also increased survival. In some cases, the disease unfortunately causes secondary tumors in other organs, that is, metastases. Treating the latter is a major challenge facing clinical oncology, especially when the brain is affected. Cases are increasing while the therapeutic options that are available remain limited.

A new model for spontaneous metastases in the brain
The absence of experimental models accurately representing the situation experienced by patients is a major obstacle to research in this field. Professor Curzio Rüegg’s team, working with groups of researchers from the universities of Bern, Bordeaux, and Lausanne, CHUV, the Ludwig Institute, and the Swiss Institute of Bioinformatics in Lausanne, has just published a study that both fills that gap and proposes new therapeutic approaches.

The main author of the study, Dr. Girieca Lorusso, along with her collaborators, first developed a new model of brain metastases for a subtype of breast cancer called “triple negative.” This model is unique because it spontaneously reproduces the steps of the metastatic process leading to the brain, as is seen in patients. By combining techniques in functional genomics, experiments in cellular and animal biology, and genetic and pharmacological  treatments, Dr. Lorusso and her team have discovered a class of molecules found at the surface of cancerous cells, connexins, that are responsible for a new mechanism of metastasization. Connexins work by activating an intracellular molecule (called FAK, for Focal adhesion kinase) that then coordinates other molecular activities enabling tumor cells to survive their “trip” to the brain and the latter’s colonization once the tumor cells are there.

New therapeutic approaches
By inhibiting a series of molecules involved in this mechanism, FAKs in particular, the researchers were able not only to prevent the formation of brain metastases, but also to stop their progress in mice. They have furthermore identified a second molecule, the PDGF receptor; inhibiting this molecule likewise showed encouraging therapeutic effects. Because certain PDGF inhibitors are currently under clinical development and PDGF receptor inhibitors are already being used in certain cancer treatments, there is hope that their anti-metastatic effects will be quickly tested in clinical studies. Both original and remarkable, these results point to new therapies on the horizon with the aim of improving care for patients with brain metastases due to breast cancer.

The study has just been published in the journal Science Translational Medicine.