RNA-seq analysis of SMARCA4-deficient NCI-H838 xenograft tumors treated with PRT3789, docetaxel, nab-paclitaxel, or combination regimens
The goal of this study was to examine transcriptional responses to the SMARCA2-selective degrader PRT3789, standard chemotherapies, and their combinations in SMARCA4-deficient NCI-H838 xenograft tumors. Six treatment groups were evaluated: (1) vehicle control, (2) PRT3789, (3) docetaxel, (4) nab-paclitaxel, (5) PRT3789 plus docetaxel, and (6) PRT3789 plus nab-paclitaxel. RNA-seq was performed on tumors collected 120 hours post–first dose to investigate treatment-specific gene expression signatures. Overall design: Female NOD/SCID mice bearing NCI-H838 xenografts were randomized into six groups (n=3 per group) and treated as follows: Group 1: Vehicle for PRT3789 (s.c., Day 0 and Day 3) plus saline (i.v., Day 0) Group 2: PRT3789, 100 mg/kg (10 mg/mL, 10 mL/kg, s.c., Day 0 and Day 3) Group 3: Docetaxel, 25 mg/kg (2.5 mg/mL, 10 mL/kg, i.v., Day 0) Group 4: Nab-paclitaxel, 30 mg/kg (3 mg/mL, 10 mL/kg, i.v., Day 0) Group 5: PRT3789, 100 mg/kg (s.c., Day 0 and Day 3) plus docetaxel, 25 mg/kg (i.v., Day 0) Group 6: PRT3789, 100 mg/kg (s.c., Day 0 and Day 3) plus nab-paclitaxel, 30 mg/kg (i.v., Day 0) The in vivo study and RNA-seq were conducted by Crown Bioscience. Tumors were harvested from all groups 120 hours after the first dose. RNA was extracted, libraries were prepared, and sequencing was performed by Crown Bioscience. Downstream analysis was performed using Pluto Bio (https://pluto.bio).