Brain metastasis (BrM) represents the most common intracranial malignancy, arising in up to 30% of all adult cancer patients and contributing significantly to cancer-related morbidity and mortality. BrM is now recognized as a biologically distinct condition with unique mechanisms of organotropism, colonization, and therapeutic vulnerability. We highlight recent progress in omic and spatial profiling, which has revealed key drivers of brain tropism. These findings have reshaped therapeutic strategies, leading to clinical trials that specifically address central nervous system (CNS) involvement. Emerging approaches now include efforts to prevent brain relapse. Preclinical models increasingly provide sophisticated platforms to evaluate next-generation therapies. Collectively, these advances are transforming the clinical landscape, offering new hope for the prevention and management of BrM through precision medicine and integrated therapeutic strategies.
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