title: Systemic treatment of hepatocellular carcinoma: dawn of a new era?
abstract: OBJECTIVE
  Despite decades of efforts by many investigators, systemic chemotherapy or hormone therapy have failed to demonstrate improved survival in patients with advanced hepatocellular carcinoma (HCC). On the basis of placebo-controlled, randomized phase III trials, sorafenib has shown improved survival benefits in advanced HCC and has set a new standard for future clinical trials. The successful clinical development of sorafenib in HCC has ushered in the era of molecularly targeted agents in this disease, which is discussed in this educational review.
  
  
  CONCLUSIONS
  Ongoing studies are evaluating the efficacy and tolerability of combining sorafenib with erlotinib and other targeted agents or chemotherapy. Many molecularly targeted agents that inhibit angiogenesis, epidermal growth factor receptor, and mammalian target of rapamycin are at different stages of clinical development in advanced HCC. Combining targeted agents that inhibit different pathways in hepatocarcinogenesis is an area of active investigation. Future research should continue to unravel the mechanism of hepatocarcinogenesis and to identify key relevant molecular targets for therapeutic intervention. Identification and validation of potential surrogate and predictive biomarkers holds promise to individualize patients' treatment to maximize clinical benefit and minimize the toxicity and cost of targeted agents. We hope that we will continue to improve the efficacy of systemic therapy in advanced HCC in the coming years.
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. azhu@partners.org
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002986:Clinical Trials as Topic; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor