As shown in the schematic illustration model (Fig. 9), the mechanistic studies implied that DTLL combinational treatment might not only prevent neoplastic proliferation via blockage of ATK/mTOR signaling and anti-apoptotic proteins (Bcl-2 and MCL1) mediated by impaired NF-κB function if given to SMAD4-sufficient/gemcitabine-sensitive PDAC cells, but also restore the bioactivity of SMAD4 as a tumor suppressor to trigger its downstream NF-κB-regulated signaling of cell apoptosis in SMAD4-deficient/gemcitabine-resistant tumors. The gene discussed is BTK; the disease is neoplasm.