If there is synergistic interaction between these therapies, a lower dose of the drugs can be used to minimize negative side effects, and more importantly, to enhance efficacy as well as to repress potential drug resistance.20 In the case of advanced HCC, it is known that Sorafenib can synergize with agents to suppress the STAT3 signaling to enhance its inhibition of upstream kinases including Raf and other receptor tyrosine kinases.19, 32 The exact mechanism for such synergy is not clear. Here, RAF1 is linked to hepatocellular carcinoma.