title: Hepatocellular carcinoma and liver transplantation: clinical perspective on molecular targeted strategies.
abstract: Hepatocellular carcinoma (HCC) has an aggressive clinical course with frequent recurrence and metastasis. Orthotopic liver transplantation has been the only curative tool for unresectable HCC; therefore, recent advances in molecular targeted therapy may improve the prognosis of HCC. The multiple kinase inhibitor sorafenib and the macrolide antibiotic rapamycin are currently the most promising agents for treating unresectable HCC. A large population-based clinical trial revealed that sorafenib significantly prolonged the overall survival of HCC patients. However, subsequent clinical studies showed that sorafenib rarely reduced tumor volume and inadequately prolonged survival of patients with severe liver damage. To improve its therapeutic effect, the development of a predictive biomarker and a sorafenib-based combination is awaited. Another molecular targeting agent, rapamycin, has now been considered as a putative agent for preventing tumor recurrence in post-liver transplantation HCC patients, because it not only has immunosuppressive activity but also exerts an anti-tumor effect. In the near future, a combination of molecular targeting agents, such as sorafenib and rapamycin, may become a standard protocol for treating unresectable HCC. For specifying cases with more effective and less harmful modalities, further investigation in clinical and basic research to identify unexpected effects are needed.
authors.affiliation: Department of Medical Technology, Niigata University Graduate School of Health Sciences, 2-746 Asahimachi-dori, Niigata 951-8518, Japan. yasunobu@med.niigata-u.ac.jp
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ichida
authors.forename: Manabu
authors.initials: M
authors.lastname: Fukumoto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D016031:Liver Transplantation; D058990:Molecular Targeted Therapy; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D011725:Pyridines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D015398:Signal Transduction; D020123:Sirolimus / Q000627:therapeutic use; D000077157:Sorafenib; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007166:Immunosuppressive Agents; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; C546842:MTOR protein, human; D019908:Proto-Oncogene Proteins c-raf; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus