Importantly, DYRK1B targeting abolished GLI1 expression in SMO-inhibitor sensitive and SMO-inhibitor resistant cells including SUFU deficient medulloblastoma, GLI1-dependent pancreatic cancer [16, 23] and Ewing sarcoma cells expressing GLI1 in response to the EWS-FLI1 oncoprotein [24, 44]. Here, EWSR1 is linked to familial pancreatic carcinoma.