Fig. 6: Targeting OLIG2 abrogates tumour initiation and relapse in vivo.
From: OLIG2 mediates a rare targetable stem cell fate transition in sonic hedgehog medulloblastoma
a Treatment strategy and H&E staining of Ptc mouse hindbrains treated with 20 mg/kg CT-179 or vehicle daily by IP injection from P3–P21 and sacrificed at P22. Lesion is indicated by the black arrow. n = 4 for CT-179, n = 4 for vehicle. b Treatment strategy and Kaplan–Meier survival curve of Ptc mice treated with 20 mg/kg CT-179 (Vehicle: n = 12; CT-179: n = 8). The dotted lines represent the duration of treatment of vehicle or CT-179 by daily IP injection (P3–P28). Significance was estimated using the log-rank (Mantel–Cox) test. Chi square = 5.425, p = 0.0198. c Sagittal MRI images of the brains of Ptc mice taken at age 3.5 months. The mice were treated with MCT (vehicle for GDC) from P56-P64 followed by CT-179 or vehicle from P65–P93. Tumours are indicated by the yellow arrows or yellow dotted lines. d Phase object confluence of adherently grown Ptch1+/−;Trp53−/− mouse tumour cells measured across 14 days using live cell imaging. Cells were treated with vehicle control, IC30 CT-179 (163.5 nM), 50 µM Vismodegib (GDC-0449), or a combination of CT-179 and Vismodegib; data shown are representative of three independent experiments; error bars denote mean ± SEM; two-tailed unpaired t-test; ns p ≥ 0.05, *p < 0.05, ***p < 0.001; p = 0.7291 (water vs. CT-179 at 172 h), p = 0.0365 (water vs. GDC at 172 h), p = 0.0277 (water vs. GDC + CT-179 at 172 h), p = 0.8717 (water vs. CT-179 at 184 h), p = 0.0614 (water vs. GDC at 184 h), p = 0.0101 (water vs. GDC + CT-179 at 184 h), p = 0.6868 (water vs. CT-179 at 220 h), p = 0.8109 (water vs. GDC at 220 h), p = 0.0002 (water vs. GDC + CT-179 at 220 h). e Treatment strategy (top) and H&E staining of Ptc mouse hindbrains treated with Vismodegib from P28–P35 followed by CT-179 or vehicle from P35–P61. Lesion is indicated by the black arrows. n = 4 for CT-179, n = 6 for vehicle. f Treatment strategy (below) and Kaplan–Meier survival curve of Ptc mice treated GDC followed by vehicle or 20 mg/kg CT-179. n = 16 for CT-179, n = 16 for vehicle. The dotted lines represent the durations of GDC debulking (daily gavage) (P56–P63) followed immediately by treatment with vehicle or CT-179 by daily IP injection (P64–P92). Significance was estimated using the log-rank (Mantel–Cox) test. Chi square = 5.452, p-value = 0.0195. Source data are provided as a Source Data file.
