Future research directions may include: optimization of treatment sequencing, such as using SphK inhibitors first to relieve immune suppression followed by anti-TNF therapy; combination with immune checkpoint inhibitors to form a multidimensional approach of “apoptosis induction and immune activation”; and development of precision therapies for HCC subtypes with concomitant lipid metabolism abnormalities (accounting for 30–40%). The gene discussed is TNF; the disease is hepatocellular carcinoma.