ArticleCell reports methods2025
Cortical organoid-derived models of the melanoma brain metastatic niche enable prioritization of cancer-targeting drugs.
Article in Cell reports methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Patient-derived resources for decoding and targeting brain metastases ecosystems.EMBO molecular medicine · 2026Review
- Protocol for validating drug efficacy and safety in scalable 96-well platforms of human cortical organoids and melanoma brain metastases.STAR protocols · 2026Article
- Human organoids: Fit for drug discovery?Stem cell reports · 2026Review
- Airborne particulate matter and the lung-brain axis: unraveling the neuroinflammatory cascade from alveolar irritation to microglial activation.Journal of neuroinflammation · 2026Review
- Brain capillary endothelial-like cells show altered barrier functionality and reduced transport of amyloid β in late-onset Alzheimer disease.Fluids and barriers of the CNS · 2026Article
- The neuro-immune-vascular landscape of lung cancer brain metastasis: insights from organoid models.Frontiers in immunology · 2026Review
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Authors and funding
28 authors.
Funding
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Abstract
Effective systemic therapies against brain metastases are severely limited. To understand and target vulnerabilities of human metastases in a brain niche context, we developed reproducible melanoma brain metastasis (MBM) models for metastasis-integrating drug screening. We co-cultured A375 melanoma cells or tumor regional lymph node-derived disseminated cancer cells (DCCs) in close proximity with human induced pluripotent stem cell-derived cortical organoids (hCOs). In these, RNA sequencing revealed an upregulation of metastasis-associated features. First, A375 cells and DCCs were screened against an anti-cancer library containing 315 compounds. Hits were ranked by neurotoxicity, central nervous system permeation, and anti-DCC efficacy. Only a minority of hits effectively targeted A375-MBMs, with the first-in-class XPO1 inhibitor selinexor emerging as top hit. Selinexor also demonstrated efficacy in DCC-MBM models and low toxicity on hCOs, suggesting a promising therapeutic window in clinically applied doses. Collectively, the MBM model provides a tool for identifying candidate therapies counteracting metastatic progression.
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