A six-year CNIO study found a short period when early brain metastases become vulnerable. Three drugs eliminated micrometastases in mice and human tissue before visible tumours formed.
The work took six years. Researchers led by the Spanish National Cancer Research Center, or CNIO, found a short stage when metastatic cells slow their aggressive behaviour as they adapt to the brain.
Three drugs eliminated early brain micrometastases in mice and human tissue before they became detectable tumours. This temporary pause may offer a target before the disease progresses or returns after surgery.
That window is not a treatment yet.
Doctors still cannot see these microscopic deposits with current diagnostic methods. No biomarker can show who carries them or who faces a defined risk. The study does identify a possible treatment window before symptoms appear.
Independent reports note that the cancers most often discussed as sources of these brain metastases include lung, breast and skin cancers, including melanoma.
Cancer Cell published the study. Manuel Valiente, head of the CNIO Brain Metastasis Group, led the project. More than 70 researchers from about 20 institutions in Spain, the United Kingdom, Germany, France and the United States took part.
RTVE also reported on the six-year project, its international scale and Valiente's leadership.
The team calls the new phase a "proliferative pause". Cells that reach the brain from tumours such as those in the lung, breast or skin enter a hostile environment. Many die there.
The cells that survive change course.
They stop acting like a tumour that is multiplying quickly. For a time, they focus on adapting to the brain instead.
That change creates the weak point. Pedro García-Gómez, the study's first author, said the researchers found active molecular mechanisms in micrometastases that clinical tests could not detect.
The team then tested three drugs that target those mechanisms. In animal models, the treatment stopped the cells from finishing their adaptation. The early deposits were destroyed.
The reported treatment strategy is based on interrupting the cells’ adaptation to the brain environment, rather than waiting for a clinically visible metastatic tumour to form. MedicalXpress described the experiments as involving three drugs tested in animal models, while stressing that the finding remains preclinical.
The evidence did not come only from mice. The CNIO group examined human material from two large tumour research networks. Each network served a different part of the validation work.
Autopsy samples from the British PEACE consortium showed micrometastases that had been too small to detect while the patients were alive. The samples let researchers examine the molecular profile of metastatic cells as they colonised the brain.
The team then turned to living tissue from Spain's RENACER network. Valiente created the network in 2021. Researchers used tissue from fully developed brain metastases removed during neurosurgery to test the treatment's effect.
The same molecular behaviour appeared at the advancing edge of established metastases. There, cells spread along the walls of blood vessels around the tumour.
This points to another use.
The drugs could target invasive cells left after surgery. That may reduce the chance of a later recurrence.
CNIO researchers are now comparing the three drugs to find the strongest combination. Their medium- and long-term goal is to start clinical trials aimed at preventing brain metastasis.
A parallel effort is looking for biomarkers that can detect deposits missed by current techniques. Research on this hidden stage was also reported earlier in connection with the search for treatment targets.
The study does not offer an immediate clinical solution. Two of the three drugs already have approval for other indications. Their use against micrometastases still needs more testing, along with the right combination.
Until biomarkers show which patients may benefit, prevention remains a research goal. It is not an available treatment.
The CNIO study shifts attention to the brief adaptation phase before a brain tumour becomes visible. The most useful intervention may begin before symptoms appear and before scans show disease.
