For example, (i) genetic mutations in COX2, EGFR, HBEG, ST6GALNAC5 (9), and MMP2, 3, 9 are found to be associated with the increased ability to penetrate the BBB (6, 10), particularly for breast cancer, the most studied primary cancer type in relevance to brain metastasis; and (ii) enhanced expressions of IL1b, HES5 (11), PCDH7 (12), γ-aminobutyric acid-related genes (13), and the activated Notch signaling pathway (7) can increase the ability of the arriving cancer cells to survive in the brain microenvironment. The gene discussed is HES5; the disease is cancer.