Fig. 4
From: Patient derived organoids to model rare prostate cancer phenotypes
High-throughput drug screening in organoids identifies novel single agents and combination therapies for CRPC-NE. a High-throughput drug screen in CRPC-NE organoids (OWCM154 OWCM155) vs control CRPC-Adeno organoids (MSK-PCA3 MSK-PCA2). The y-axis is the AUC (area under the curve) differential of the mean of the CRPC-NE samples – the mean of the CRPC-Adeno samples. Compounds indicated in red are specific for CRPC-NE while compounds indicated in blue are specific for CRPC-Adeno. Highlighted compounds are clinically relevant and represent a subclass of drugs. b High-throughput drug screen single agent analysis of differences in sensitivity within the CRPC-NE samples. c Cell viability assay using vehicle or different doses of cobimetinib in OWCM154 and OWCM155 (n = 9, for each treatment dose, error bars: s.e.m.), two-way ANOVA test is used. ****p < 0.0001. d High-throughput drug combination screen in CRPC-NE organoids (OWCM154, OWCM155) vs CRPC-Adeno organoids (MSK-PCA3, MSK-PCA2). GSK503 has been added to the drug screening plate at IC30. The y-axis is the AUC differential of the mean of the CRPC-NE samples – the mean of the CRPC-Adeno samples. Compounds indicated in red are more effective for CRPC-NE in combination with GSK503 while compounds indicated in blue are more effective for CRPC-Adeno in combination with GSK503. e Cell viability assay for high-throughput drug combination screen validation. Organoids are treated with a fixed dose of GSK343 (5 μM) and escalated doses of alisertib. The organoids treated with alisertib in combination with GSK343 are represented with a black line while the organoids treated with alisertib plus DMSO are represented in blue (n = 9, for each treatment dose, error bars, s.e.m.). Two-way ANOVA test is used. Alisertib-GSK503 combination in OWCM154 has p < 0.00.27, (**) while in MSK-PCA3 is not significant (ns)
