We speculate that DTLL seems to act as a module of the SMAD4 driver that normalizes its function as a tumor suppressor according to SMAD4 protein level and genetic status in PDAC, and then adjusts NF-κB, TRIM33, gemcitabine-metabolic enzymes (such as RRM2) and proteomic profiles of PDAC cells, which explains the synergistic effect on tumor growth of DTLL in combination with gemcitabine. This evidence concerns the gene NFKB1 and neoplasm.