title: Systemic therapy for advanced hepatocellular carcinoma: past, present, and future.
abstract: BACKGROUND
  Although approximately 80% of hepatocellular carcinoma (HCC) cases occur in developing countries, the incidence of HCC in Western countries is on the rise due to the impact of hepatitis C. Challenges in developing effective therapies include the inherent chemoresistance of HCC, the pharmacologic challenges presented by a diseased liver, the presentation of most patients at advanced stages, and the difficulty in adequately measuring radiological response. While responses to traditional chemotherapeutic agents have been documented, significant survival benefit is debatable.
  
  
  METHODS
  The authors review the results of published clinical trials of systemic therapy and immunotherapy that have impacted the present treatment of HCC.
  
  
  RESULTS
  With recent progress in the elucidation of HCC molecular pathways, targeted agents show promise. The multikinase inhibitor sorafenib has provided survival benefit in patients with advanced HCC and well-preserved liver function. Sunitinib, bevacizumab, epidermal growth factor receptor inhibitors, and mammalian target of rapamycin (mTOR) inhibitors have shown activity in small patient cohorts. Immunotherapy appears to be a promising approach that can result in the regression of bulky, invasive cancer in some patients.
  
  
  CONCLUSIONS
  New agents with a variety of mechanisms of activity offer promising therapeutic options for patients with advanced HCC.
authors.affiliation: Gastrointestinal Tumor Program, Moffitt Cancer Center, Tampa, FL 33612, USA. Jennifer.Giglia@moffitt.org
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Giglia
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Antonia
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Berk
authors.forename: Salvador
authors.initials: S
authors.lastname: Bruno
authors.forename: Sophie
authors.initials: S
authors.lastname: Dessureault
authors.forename: Steven E
authors.initials: SE
authors.lastname: Finkelstein
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000175:diagnosis / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents