Patient-derived resources for decoding and targeting brain metastases ecosystems

Abstract Brain metastases (BrM) affect up to 30% of patients with solid tumors, yet durable intracranial control remains rare, and the biological drivers of this poor prognosis are incompletely understood. Patient-derived resources, such as clinical cohorts, biobanks, functional ex vivo models, and multi-omic platforms, are central to closing this gap, but their generation and integration face substantial logistical and technical hurdles. Drawing on the RISEbrain consortium's experience, this Perspective examines BrM-focused cohorts and biobanks, highlighting the underused potential of rapid autopsy programs to capture early metastatic seeding. We discuss patient-derived organotypic cultures and emerging organoid-based "avatar" systems as functional platforms for therapeutic profiling, alongside the complementary strengths of bulk and single-cell/-nucleus transcriptomics. We outline how spatial transcriptomics and proteomics are resolving the architecture of the BrM microenvironment, and assess liquid biopsy approaches, including emerging photonic biosensors, for non-invasive monitoring. Together, these resources form an interdependent toolkit whose coordinated deployment will advance early detection, prevention, and precision treatment of BrM.