Fig. 3

Heterogeneity in drug sensitivity in recGSCs. a Dose–response curves of the pan-HER inhibitor canertinib display the variation in drug efficacy in the recGSC cultures. Three responses are classified below the threshold for moderate activity (DSS ≥ 10). b Distribution of the number of drugs displaying a DSS ≥ 10 across the recGSC cultures. c Using a non-parametric one-way ANOVA of ranks, a significant difference was observed in the overall drug sensitivity across the cultures (p < 0.0001). According to the individual culture’s sensitivity to the entire drug collection (n = 525 drugs), they separated into two major clusters as the most and least sensitive. d Clustering of recGSC cultures by correspondence analysis based on all drug responses (n = 525) in all tumors (n = 6). The dots in the scatter plot represents the drugs in the DSRT and the color shading represent a heat map of where the average of the data is located. The scattering of tumors in the plot display both how they differ from the average and how tumors cluster together based on similarities in drug sensitivity patterns. e In the DSRT there were four pan-HER inhibitors that displayed a DSS ≥ 10 in recGSC cultures. f The consistency of T1532 being the most sensitive and T1544 the most resistant displayed an excellent correlation in correlation matrices (Spearman, ρ). g p-values in the correlation matrix of the pan-HER inhibitors. h Selecting for drugs with at least moderate efficacy (DSS ≥ 10) and increased patient-selectivity (sDSS_GBM ≥ 5) the distribution of individual classes of drugs with selective efficacy revealed a considerable tumor heterogeneity in drug sensitivity in recGSC cultures