This finding, published in the journal Cancer Cell, opens a potential route to stopping the disease before it becomes clinically apparent, advancing towards metastasis prevention. A similar strategy could also be used to prevent relapse after surgery.
The study, led by Manuel Valiente, head of the Brain Metastasis Group at CNIO, in collaboration with the Centre for Genomic Regulation (CNAG) and around twenty international institutions, investigated the earliest stages of metastatic cell establishment in distant organs.
The researchers have demonstrated, in both mice and human brain metastasis samples, that these micrometastases can be eliminated using three drugs, two of which are already approved for other indications. However, this approach is not yet feasible in clinical practice due to the lack of diagnostic tests capable of detecting micrometastases or reliable biomarkers.
CNAG's Spatial Genomics Team conducted in situ single-cell analyses of human brain samples with micrometastases using Xenium (10x Genomics). This analysis helped identify the molecular features of these early lesions and their state during the 'proliferative pause'.
Anna Pascual-Reguant, Spatial Genomics Team Leader at CNAG, explains that "understanding how tumor cells behave in tissues and the mechanisms that regulate them is essential to better understand tumor biology before metastasis develops."
Although the study focused on brain metastasis, the authors hypothesize that this vulnerable stage may be common to the metastatic process more broadly and intend to investigate this in future studies.
