Combined MEK and JAK/STAT3 pathway inhibition effectively decreases medulloblastoma tumor progression.

RNA sequencing was carried out to identify the signaling pathways and hallmarks that change following MEK and/or JAK/STAT3 pathway inhibition. (1) 2.5x10^5 UI226 cells were injected into the cerebellums of NOD SCID mice. Mice were treated with either vehicle controls of selumetinib twice daily (drug holiday on the weekend) via oral gavage. Tumor were extracted at endpoint and human cells were isolated by FACS with HLA. Human cells from vehicle and selumetinib treated xenografts were subject to RNA-seq. (2) We performed RNA sequencing on selumetinib and/or pacritinib treated UI226 tumorspheres (N=4-6 biological replicates for each condition) to characterize the sustained transcriptomic changes 5 days following treatment in vitro. Tumorspheres were treated with vehicle, selumetinib only, pacritinib only or selumetinib + pacritinib