Since GLI activator function is critical for tumor-initiating cells [16, 25, 25, 57] and also involved in the development of Ras-driven murine pancreatic cancer within the epithelial tumor compartment [23, 47, 55], we speculate that chemical DYRK1B inhibition may be able to repress the growth of pancreatic cancer due to negative regulation of SMO-independent GLI1 in tumor and tumor-initiating cells, consistent with the abrogation of tumor engraftment in response to genetic DYRK1B inhibition. Here, DYRK1B is linked to familial pancreatic carcinoma.