The National Genomic Analysis Centre (CNAG) has participated in a study led by the National Cancer Research Centre (CNIO) that has developed a new strategy to prevent brain metastasis. The research, published in the journal Cancer Cell, opens a potential avenue to halt the disease before it manifests clinically, which could facilitate its prevention. A similar strategy might also be useful for preventing relapses after surgical intervention.
Researchers studied the early stages of metastatic cell establishment in distant organs and discovered a transient phase, known as a 'proliferative arrest,' during which these cells are particularly vulnerable. The study was led by Manuel Valiente, head of the Brain Metastasis Group at CNIO, with contributions from the Spatial Genomics team at CNAG, which performed key single-cell analyses with spatial resolution on brain samples from patients with micrometastases.
According to the authors, the results 'open a window of opportunity to attack the disease before symptoms appear,' states Valiente. This discovery marks the beginning of a race to prevent metastasis and lays the groundwork for developing strategies to prevent its recurrence after surgical removal.
Researchers demonstrated in mice and human samples that these micrometastases can be eliminated with three drugs, two of which are already approved for other uses. However, this approach is not yet clinically applicable due to the lack of diagnostic tests to detect micrometastases and reliable biomarkers to identify at-risk patients. The next step will involve clinical trials to evaluate the efficacy of the drugs and identify biomarkers.
Cancer cells colonizing a new organ must adapt to an environment different from the original tumor. Many die during this process, but those that survive enter a 'proliferative arrest,' a period where they seek ways to survive and temporarily abandon their aggressive behavior.
The Spatial Genomics team at CNAG conducted in situ single-cell analyses on human brain samples with micrometastases using Xenium (10x Genomics). This analysis helped identify the molecular characteristics of these early lesions and their state during proliferative arrest.
Dr. Anna Pascual-Reguant, head of the Spatial Genomics team at CNAG, explains that 'understanding how tumor cells behave in tissues and the mechanisms that regulate them is essential for better comprehending tumor biology before metastasis develops.' Studying these early stages can help identify the changes that allow cancer cells to adapt and progress, thereby improving patient outcomes.
Although the study focused on brain metastases, the authors hypothesize that this vulnerable phase could be common to the metastatic process in general, a question they plan to investigate in future work.
