Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling

被引:1152
作者
Wilhelm, Scott M. [1 ]
Adnane, Lila [1 ]
Newell, Philippa [2 ]
Villanueva, Augusto [2 ,3 ]
Llovet, Josep M. [2 ,3 ]
Lynch, Mark [1 ]
机构
[1] Bayer HealthCare Pharmaceut, Montville, NJ 07045 USA
[2] Mt Sinai Sch Med, Div Liver Dis, Mt Sinai Liver Canc Program, New York, NY USA
[3] Hosp Clin Barcelona, CIBERehd, Inst Invest Biomed August Pi i Sunyer, Liver Unit,Barcelona Clin Liver Canc Grp, Barcelona, Spain
关键词
D O I
10.1158/1535-7163.MCT-08-0013
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Although patients with advanced refractory solid tumors have poor prognosis, the clinical development of targeted protein kinase inhibitors offers hope for the future treatment of many cancers. In vivo and in vitro studies have shown that the oral multikinase inhibitor, sorafenib, inhibits tumor growth and disrupts tumor microvasculature through antiproliferative, antiangiogenic, and/or proapoptotic effects. Sorafenib has shown antitumor activity in phase II/III trials involving patients with advanced renal cell carcinoma and hepatocellular carcinoma. The multiple molecular targets of sorafenib (the serine/threonine kinase Raf and receptor tyrosine kinases) may explain its broad preclinical and clinical activity. This review highlights the antitumor activity of sorafenib across a variety of tumor types, including renal cell, hepatocellular, breast, and colorectal carcinomas in the preclinical setting. In particular, preclinical evidence that supports the different mechanisms of action of sorafenib is discussed. [Mol Cancer Ther 2008;7(10):3129-40]
引用
收藏
页码:3129 / 3140
页数:12
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