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In people suffering brain metastasis, cognitive impairment has been traditionally thought to result from the mass effect of the tumor growth.  Recently, we teamed with the group of Manuel Valiente (CNIO), to discover that different experimental models of brain metastasis actually co-opt neuronal activity (Sanchez-Aguilera et al., Cancer Cell 2023). We recorded brain activity in the vicinity of metastases from various primary sources and oncogenomic profiles. Using data science and machine learning, we found that a model trained in electrophysiological signals surrounding the three different brain metastasis can help to disambiguate between subtypes, and to anticipate their progression early in advance. These alterations were linked to changes in the density of GABAergic inhibitory synapses and specific transcriptional programs. Our results pave the way to investigate the functional signatures of the crosstalk between cancer cells and the surrounding neuronal circuit as a potential translational biomarker.

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