A new way to prevent metastasis in breast cancer has been discovered.

PalmA study by the Hospital del Mar Research Institute, with the participation of the Oncology and Pathology Departments, researchers from the Spanish Breast Cancer Research Group (GEICAM) and led by the Mallorcan researchers Toni Celià-Terrassa and Catalina Rozalén has found a new way to stop the breast cancer metastasis, at the time of micrometastasis. That is, when the first cells reach other organs. The work has identified the role of the TIM-3 protein in the most aggressive cells that initiate metastasis. The TIM-3 protein allows tumor cells to suppress the immune system when they reach distant organs, thus ensuring their survival at a critical moment. This fact makes it a moment of therapeutic opportunity and turns TIM-3 into a "unique and specific" therapeutic target for this "precise moment" of the disease.

The discoveries made open up the possibility of using drugs that block the action of TIM-3 to prevent the appearance of new tumors. "Having tools for these high-risk patients, such as those who are TIM-3 positive, may allow us to apply anti-TIM3 therapy after surgery to avoid subsequent relapse and prevent metastasis," says Dr. Celià-Terrassa, a researcher at the Cancer Stem Cells and Dynamics Research Group. This preclinical study indicates that treatment should be applied before the onset of metastasis because once the disease has occurred, it is more difficult to control and TIM-3 loses its relevance, the experts say. "First, however, it is necessary to develop relevant clinical trials to validate the possibility of using existing treatments to inhibit this protein in TIM-3-bearing cells before and after surgery," the press release explains.

Attacking at the first moments

The time at which cells arrive at the new organ is critical, but little known because there are no clinical manifestations or techniques that allow its investigation. The team responsible for this study used mice to describe the role of TIM-3 in the survival of the first tumor cells that invade the affected organs. "This is a vulnerable phase of the disease, since few cells remain, and if we understand what happens and are able to eradicate them, we will have a great opportunity to prevent clinical metastasis, which is the dangerous phase of the disease," explains Celià-Terrasa. This is the first time that this function of TIM-3 and its relationship with cancer cells has been identified.

Tumor cells that survive the journey from the breast to the new organ from the primary tumor use TIM-3 to avoid attack by the immune system. They thus manage to reconfigure the immune system of the new organ they reach to avoid attack by immune cells and survive. This allows them to proliferate and generate a new tumor, the initiation of metastasis, as researchers have been able to observe with cells from different types of breast cancer that have metastasized to the liver. Furthermore, with a sample of patients from Hospital del Mar, they were able to verify that those patients with tumors with high levels of TIM-3 had a higher risk of metastasis and a poor prognosis. "Patients who are positive for TIM-3 in their primary tumor have a higher risk of recurrence and metastasis," says Dr. Catalina Rozalén, a predoctoral researcher at the Hospital del Mar Research Institute. "Breast cancer is diagnosed before it can be detected," adds Dr. Joan Albanell, head of the Oncology Department at Hospital del Mar and a researcher at his research institute, at GEICAM, and at the Cancer Department of Ciber (Ciberón). "Blocking TIM-3 may allow us to achieve this, but a lot of research in appropriately designed clinical trials is still needed to get there," he says.