Astrocyte heterogeneity in brain metastases.

Brain metastasis is increasingly understood as a disease of reciprocal adaptation between metastatic cells and the brain microenvironment. Among host cells, astrocytes have emerged as central regulators of metastatic colonization, survival, immune remodeling, and treatment resistance. Recent studies are re-defining astrocytes to explore the functional implications of their cellular heterogeneity. Evidence in brain metastasis indicates that astrocyte responses are heterogeneous across anatomical space, stage of colonization, and tumor type. This framework helps explaining how distinct astrocyte programs can coexist and why no single experimental platform captures their organization and complex biology. Moving toward spatially resolved, longitudinal, and functionally validated definitions of astrocyte states could clarify mechanisms and guide more precise therapeutic opportunities in brain metastasis. In this Viewpoint, we examine studies that have challenged the long-standing paradigm of astrocytes as a uniform entity, highlighting how recent technological advances reinforce previous findings and pave the way for identifying new therapeutic targets.