Molecular profiling of ex vivo prostate cancer CAF models captures stromal heterogeneity and drug vulnerabilities

We performed comprehensive multi-omics profiling of primary CAFs derived from seven PCa patients, integrating single-cell RNA sequencing (scRNA-seq) and drug sensitivity and resistance testing (DSRT). CAF cultures were established ex vivo from primary tumor tissues, and scRNA-seq was used to characterize cellular subpopulations. DSRT was applied to evaluate responses to 526 oncology compounds, focusing on pathway-specific inhibition. This study provides a high-resolution landscape of CAF heterogeneity in PCa, uncovering distinct subpopulations with unique vulnerabilities. The identification of actionable drug sensitivities supports the development of stromal-directed therapies targeting CAFs to disrupt tumor-stroma crosstalk and improve treatment outcomes in PCa. Files: - CAF_metadata: metadata for the scRNA-seq data - CAF_counts: raw counts for the scRNA-seq data - CAF_RNA_clusters.csv: Assigned Leiden-clusters for each CAF - Suppl.source data.xlsx: Suppl source data for supplementary figures 1, 3A, 3B