STAT3 and hepatocellular carcinoma: STAT3 can be directly suppressed by small molecule compounds like static,275 OPB-111077,276 OPB-31121,277 napabucasin 278, and siRNA (AZD9150).279 OPB-111077 was well tolerated overall while showed limited efficacy in sorafenib-refractory HCC patients.276 OPB-31121 in a phase I research of advanced solid tumors (NCT00657176) and HCC (NCT01406574)277,280 showed limited antitumor efficacy with toxic side effects.