title: Sorafenib suppresses postsurgical recurrence and metastasis of hepatocellular carcinoma in an orthotopic mouse model.
abstract: Surgical resection is the first-line treatment for hepatocellular carcinoma (HCC) patients with well-preserved liver function. Nevertheless, the rate of postoperative recurrence at 5 years is as high as 70%, and this gravely jeopardizes the therapeutic outcome. Clearly, new approaches are needed for preventing the relapse of this deadly disease. Taking advantage of a luciferase-labeled orthotopic xenograft model of HCC, we examined the role of sorafenib, the first systemic drug approved for advanced HCC patients, in the prevention of HCC recurrence. We found that sorafenib suppressed the development of postsurgical intrahepatic recurrence and abdominal metastasis and consequently led to prolonged postoperative survival of mice in this model. Furthermore, hyperactivity of extracellular signal-regulated kinase signaling caused by elevated levels of growth factors associated with postoperative liver regeneration enhanced the sensitivity of HCC cells to sorafenib; this provides a plausible explanation for the observation that recurrent tumors are more responsive to growth inhibition by sorafenib.
  
  
  CONCLUSIONS
  Our results strongly suggest that by effectively reducing postoperative recurrence, sorafenib has a potential application in early-stage HCC patients who have undergone hepatectomy with curative intention.
authors.affiliation: Center for Cancer Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yu-Xiong
authors.initials: YX
authors.lastname: Feng
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Yue-Zhen
authors.initials: YZ
authors.lastname: Deng
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Yang
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Li
authors.forename: Dong-Xian
authors.initials: DX
authors.lastname: Guan
authors.forename: Fan
authors.initials: F
authors.lastname: Yao
authors.forename: Yin-Qiu
authors.initials: YQ
authors.lastname: Zhu
authors.forename: Ying
authors.initials: Y
authors.lastname: Qin
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Meng-Chao
authors.initials: MC
authors.lastname: Wu
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Wang
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Wang
authors.forename: Shu-Qun
authors.initials: SQ
authors.lastname: Cheng
authors.forename: Dong
authors.initials: D
authors.lastname: Xie
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001557:Benzenesulfonates / Q000494:pharmacology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D000077157:Sorafenib; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D048049:Extracellular Signal-Regulated MAP Kinases