Fig. 5
PTC-derived organoids as a platform for predicting drug responses. a Protocol for the treatment of PTC organoids with various anticancer drugs. Organoids were plated (10,000 organoids/mL) and cultured for 2 days, and drugs were diluted in organoid medium and added into each well with six-point fivefold dilution series (3.2 × 10–3 µM to 10 µM). After 5 days of treatment with the drugs, organoid viability was examined by using the CellTiter-Glo® 3D Reagent. b Simplified scheme of the RAS/RAF/MEK/ERK signaling pathway including targeted drugs used. c Heatmap of logIC50 values for 13 anticancer drugs used to treat 9 PTC organoid lines by applying nonlinear regression. The corresponding colors for logIC50 are depicted in the legend. Orange indicates high IC50 values, violet indicates low IC50 values. The assay was performed with 3 biological replicates (different passages of PTC organoids). d Representative scatterplots of 1-AUC values generated from two biological replicates of the drug screening data. Each data point represents 1-AUC for a drug used to treat the indicated PTC organoids. Passage numbers of PTC organoid lines were: PTC-1_O, P3, P4 and P5; PTC-2_O, P2, P3 and P4; PTC-3_O, P3, P4 and P5; PTC-4_O, P3, P4 and P5; PTC-5_O, P3, P4 and P5; PTC-6_O, P3, P4 and P5; PTC-7_O, P4, P5 and P6; PTC-8_O, P3, P4 and P5; PTC-9_O, P4, P5 and P6