Sorafenib suppresses postsurgical recurrence and metastasis of hepatocellular carcinoma in an orthotopic mouse model
- 12 November 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of Hepatology
- Vol. 53 (2), 483-492
- https://doi.org/10.1002/hep.24075
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. Conclusion: 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. (HEPATOLOGY 2011;53:483‐492)This publication has 30 references indexed in Scilit:
- Characterisation of a novel cell line (CSQT-2) with high metastatic activity derived from portal vein tumour thrombus of hepatocellular carcinomaBritish Journal of Cancer, 2010
- Gene Expression in Fixed Tissues and Outcome in Hepatocellular CarcinomaThe New England Journal of Medicine, 2008
- Sorafenib in Advanced Hepatocellular CarcinomaThe New England Journal of Medicine, 2008
- Hepatocellular Carcinoma: Epidemiology and Molecular CarcinogenesisGastroenterology, 2007
- Phase II Study of Sorafenib in Patients With Advanced Hepatocellular CarcinomaJournal of Clinical Oncology, 2006
- Spreds, inhibitors of the Ras/ERK signal transduction, are dysregulated in human hepatocellular carcinoma and linked to the malignant phenotype of tumorsOncogene, 2006
- Mitogen-Activated Protein Kinase Pathways Mediated by ERK, JNK, and p38 Protein KinasesScience, 2002
- Role of angiogenesis in tumor growth and metastasisSeminars in Oncology, 2002
- Cutaneous Wound HealingThe New England Journal of Medicine, 1999
- Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a lewis lung carcinomaCell, 1994