Cortical organoid-derived models of the melanoma brain metastatic niche enable prioritization of cancer-targeting drugs.

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-MBM

SUBMITTER: Krieg K 

PROVIDER: S-EPMC12859518 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature