CNIO researchers found a short period when early brain metastases are unusually vulnerable. Three drugs destroyed micrometastases in laboratory models before they became detectable tumours.
Many cancer cells die soon after they reach the brain because the new environment is hostile. The cells that survive enter a temporary state that researchers call a "proliferative pause." They stop acting aggressively and begin adapting to their surroundings.
The CNIO Brain Metastasis Group studied this stage in a paper published in Cancer Cell in 2025. The work focuses on what happens before brain metastases can be found with clinical tests.
The window is brief.
Research reviewed in Neuro-Oncology places this early seeding process within a broader field studying how neuronal activity and the brain microenvironment support metastases from breast cancer, melanoma and small-cell lung cancer.
That pause gave the researchers a possible treatment window. They examined the molecular activity of micrometastases that were still too small to detect. The team found mechanisms that helped the cells stay alive.
When those mechanisms were blocked, the cells could not finish adapting to the brain. They died in animal models. The work is linked to Manuel Valiente and the CNIO Brain Metastasis Group, which has helped establish early brain-metastasis seeding as a separate area of study.
The experiments tested three medicines against molecular targets involved in the process. Two are already approved for other medical uses. All three worked in the tested models and destroyed the micrometastases before they became visible metastases.
The project lasted six years. Manuel Valiente led the work as head of the CNIO Brain Metastasis Group. More than 70 researchers from around 20 institutions in Spain, the United Kingdom, Germany, France and the United States took part.
The findings appeared in Cancer Cell as part of a peer-reviewed research programme. They were not presented as a single isolated laboratory result.
CNIO is also involved in the development of Spain’s national cancer data node. That infrastructure is intended to connect cancer-related data and accelerate translational research, providing a broader institutional context for the centre’s work on brain metastasis.
Human samples were central to the validation work. The British PEACE consortium supplied samples from tumours and deceased patients. Those samples let researchers examine metastases that had been too small to detect clinically.
The CNIO then used living samples from RENACER, the Spanish National Brain Metastasis Network created by Valiente in 2021. The team confirmed the therapeutic effect in those samples.
The same molecular pattern appeared at the advancing edge of established human metastases. Invasive cells spread by attaching themselves to the walls of blood vessels around the metastatic growth. The researchers say the medicines that target the vulnerable pause can also restrain these invasive fronts.
For readers following medical developments from Spain, an earlier health report offers a separate example of research and policy affecting treatment access. The CNIO study is different. Its immediate result is experimental evidence, not a treatment already available to patients.
Manuel Valiente describes the discovery as the beginning of a race to prevent metastasis. The current limits are clear. Doctors cannot yet identify these micrometastases with available diagnostic tests, and no biomarkers can signal the risk.
The clinical value lies in this hidden interval. Recent neuro-oncology literature says brain metastases are often found only after they become clinically apparent. The earliest period of tumour-cell adaptation may offer the best chance to intervene.
The next steps are practical. The team must determine which combination of the tested medicines offers the greatest therapeutic benefit. It must also develop biomarkers for the hidden disease.
Clinical trials are the medium- to long-term objective. The findings still need confirmation in independent patient cohorts.
This research has not produced a preventive treatment for routine care. It has identified a biological window in which metastatic cells can be attacked before symptoms appear. That finding moves the work closer to preventing brain metastasis and postoperative relapse, while the gap between laboratory evidence and proven patient treatment remains clear.
