Further studies implied that DTLL combinational treatment might not only prevent neoplastic proliferation via blockage of ATK/mTOR signaling and anti-apoptotic proteins mediated by impaired NF-κB function in 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 and enhance the gemcitabine-related enzyme RRM2 in SMAD4-deficient/gemcitabine-resistant tumors. The gene discussed is BTK; the disease is neoplasm.