Beyond sorafenib: novel targeted therapies for advanced hepatocellular carcinoma.
BACKGROUND
The successful approval of sorafenib has greatly stimulated the development of other molecular targeted agents in advanced hepatocellular carcinoma (HCC).


METHODS
The aim of this review was to summarize the key data of sorafenib Phase III studies and the lessons and unanswered questions with sorafenib in HCC. It extensively updated the current ongoing studies combining sorafenib with erlotinib and other targeted agents or chemotherapy, and many molecularly targeted agents under development that inhibit angiogenesis, EGFR, and mammalian target of rapamycin (mTOR).


RESULTS
A comprehensive understanding of the current status of drug development of targeted agents in advanced HCC and insights into the challenges of developing these agents in HCC.


CONCLUSIONS
Sorafenib is the first and only approved agent in advanced HCC. Several Phase III studies are ongoing with other drugs in advanced HCC. Many early clinical trials are conducted to assess other molecularly targeted agents that inhibit different pathways of hepatocarcinogenesis.
Zhu
Andrew X
AX
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA. azhu@partners.org
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000494:pharmacology / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000503:physiopathology; D017326:Clinical Trials, Phase III as Topic; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D000077157:Sorafenib
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib