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Comparing the Efficacy of Sunitinib with Sorafenib in Xenograft Models of Human Hepatocellular Carcinoma: Mechanistic Explanation.
MedLine Citation:
PMID:  21834756     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Hepatocellular carcinoma (HCC) is the fifth most common and third deadliest malignancy. Sorafenib has demonstrated 44% survival advantage over placebo and has emerged as a standard of care in advanced HCC. The therapeutic effects of sorafenib are however transient and hence additional treatment options are warranted. In this study, we aimed to compare the efficacy of sunitinib relative to sorafenib, two potent inhibitors of protein tyrosine kinases involved in tumor growth, metastasis, or angiogenesis. We reported that sorafenib and sunitinib suppressed tumor growth, angiogenesis, cell proliferation, and induced apoptosis in both orthotopic and ectopic models of HCC. However, the antitumor effect of 50 mg/kg sorafenib was greater than that of 40 mg/kg sunitinib. Sorafenib inhibited p-eIF4E Ser209, p-p38 Thr180/Tyr182 and reduced survivin expression. This was not seen with sunitinib. In addition, the antitumor and apoptotic effects of sorafenib, which are associated with upregulation of fast migrating Bim and ASK1 and downregulation of survivin, were greater than that of sunitinib. These observations explained in part the apparent superior anti-tumor activity of sorafenib compared to sunitinib. In conclusion, sunitinib demonstrated an inferior anti-tumor activity compared to sorafenib in ectopic and orthotopic models of human HCC. It remains to be seen whether such observations would be recapitulated in humans.
Authors:
Hung Huynh; Su Pin Choo; Han Chong Toh; Wai Meng Tai; Alexander Yaw Fui Chung; Pierce Kah Hoe Chow; Richard Ong; Khee Chee Soo
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-12
Journal Detail:
Title:  Current cancer drug targets     Volume:  -     ISSN:  1873-5576     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101094211     Medline TA:  Curr Cancer Drug Targets     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, 11 Hospital Drive, 169610, Singaporecmrhth@nccs.com.sg.
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