GSEA analysis of gene expression changes in AZD1208-resistant castration-resistant prostate cancer (PC) cells. A) The list of the top 10 gene sets enriched in tumor cell lines established from recurrent, castrated, AZD1208-treated mice (CxAZD) relative to cell lines established from castrated, recurrent, vehicle-treated recurrent tumors (CxVehicle). B) Enrichment analysis plots showing enrichment of genes upregulated in P53 knockdown cells (left panel) and JAK2 knockdown cells (right panel) in CxAZD tumor cell lines. C) Immunoblots showing reduced p53 protein levels in AZD1208-treated castrated Myc-CaP allograft cell lines, but unchanged p-Stat3 and Stat3 levels. D) Reduced p53 expression in AZD1208-treated Myc-CaP tumors by immunohistochemical staining both before and after castration (upper four panels), while tumors exposed to radiation treatment (XRT) or radiation plus AZD1208 (XRT/AZD) expressed high levels of p53 (bottom two panels). Scale bar = 0.05mm E) Gene expression profile of AZD1208-resistant recurrent tumor cells is associated with human prostate cancer recurrence. Cross-species Gene Set Enrichment Analysis analysis shows association of gene expression signature from AZD1208-treated recurrent tumors with biochemical recurrence in prostate cancer patients from (44).