A six-year study led by the Spanish National Cancer Research Center, or CNIO, identified a brief stage when metastatic cells slow their aggressive behaviour as they adapt to the brain. Three drugs eliminated early brain micrometastases in animal models before they became detectable tumours; the team also tested the drugs on human tissue.
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.
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 across Spain, the United Kingdom, Germany, France and the United States took part.
RTVE also covered 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 in the lung or breast, as well as skin cancers, enter a hostile environment. Many die there.
The cells that survive change course. They stop behaving like a tumour multiplying quickly. For a time, they focus instead on adapting to the brain.
That change creates the weak point. Pedro García-Gómez, the study's first author, said researchers found active molecular mechanisms in micrometastases that clinical tests could not detect.
The team then tested three drugs targeting those mechanisms. In animal models, the treatment stopped the cells from completing their adaptation. The early deposits were destroyed.
The evidence extended beyond mice. The CNIO group examined human material from two large tumour research networks, each contributing a different part of the validation work.
Autopsy samples from the British PEACE consortium showed micrometastases that had been too small to detect while 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, which Valiente created 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, where cells spread along the walls of blood vessels around the tumour.
This points to another potential use. The drugs could target invasive cells left after surgery, potentially reducing 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.
Researchers are also looking for biomarkers that can detect deposits missed by current techniques. Work on this hidden stage was reported earlier in connection with the search for treatment targets.
The study offers no immediate clinical solution. Two of the three drugs are already approved for other indications. Their use against micrometastases still needs more testing, as does the right combination.
Until biomarkers show which patients may benefit, prevention remains a research goal, not an available treatment.
