Fig. 7: MK-8776/olaparib combination impairs tumor growth in in vitro and in vivo SHH-dependent medulloblastoma models.

A–B Data analyses on medulloblastoma and normal cerebella datasets performed on the R2-Genomics platform. Box plots of PARP1 (A) and CHK1 (B) expression relative to normal cerebellum (CBL) and SHH-type medulloblastoma patients (SHH-MB). C WB analysis performed on whole extracts of young adult (P21) WT mice cerebella (CBL), Ptch-KO mice cerebella (MB Ptch^−/−) and on extracts from neurosphere cultures obtained from a Ptch-KO medulloblastoma (N-MB). D WB analysis of whole-cell lysates of N-MB neurospheres treated for 9 and 24 h. Blots were probed with the indicated antibodies; β-actin was used as loading control. The asterisk indicates the 89-kDa PARP1 cleaved fragment. Data are representative of three replicates. E WB analysis of cerebella explanted from P5 Ptch^−/− mice after i.p. injection of vehicle or olaparib. Blots were probed with the indicated antibodies; β-actin was used as loading control. F Representative images of the cerebella explanted at P9 from Ptch^−/− or WT mice, treated daily for 4 days. Dotted lines highlight the size/shape of the cerebella. G Dot plots representing the mean tumor volume (±SEM) of mice treated as above (n = 5/group, Ola n = 4). p values were calculated by ANOVA (*p < 0.05).