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

Scott M. Wilhelm, Lila Adnane, Philippa Newell, Augusto Villanueva, Josep M. Llovet, Mark Lynch

Research output: Contribution to journalReview articlepeer-review

1110 Scopus citations

Abstract

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 ofsoraf enib (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.

Original languageEnglish
Pages (from-to)3129-3140
Number of pages12
JournalMolecular Cancer Therapeutics
Volume7
Issue number10
DOIs
StatePublished - 1 Oct 2008

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