When metastatic cells face a new microenvironment different from the one at the primary tumor, a selective process of adaptation occurs. Given the heterogeneity and plasticity inherent to cancer cells, there are many possible ways to acquire the fitness to survive and colonize a secondary organ. However, after analyzing multiple experimental models of brain metastases from different cancer types, we found that only a very small number of genes were commonly altered. This suggested the existence of critical nodes necessary to metastasize to the brain perhaps in response to strong selective pressures from the microenvironment. In order to prove this hypothesis we are analyzing the functional role of these genes in the process of brain metastases.