Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling
TLDR
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.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 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.read more
Citations
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AASLD PRACTICE GUIDELINE Management of Hepatocellular Carcinoma: An Update
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Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001-2011).
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TL;DR: The purpose of this document is to assist physicians, patients, health-care providers, and health-policy makers from Europe and worldwide in the decision-making process according to evidencebased data.
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Pharmacological inhibition of cystine–glutamate exchange induces endoplasmic reticulum stress and ferroptosis
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References
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Journal ArticleDOI
Sorafenib in Advanced Hepatocellular Carcinoma
Josep M. Llovet,Sergio Ricci,Vincenzo Mazzaferro,Philip Hilgard,Edward Gane,Jean-Frédéric Blanc,André Cosme de Oliveira,Armando Santoro,Jean-Luc Raoul,Alejandro Forner,Myron Schwartz,Camillo Porta,Stefan Zeuzem,Luigi Bolondi,Tim F. Greten,Peter R. Galle,Jean Francois Seitz,Ivan Borbath,Dieter Häussinger,Tom Giannaris,Minghua Shan,M. Moscovici,D. Voliotis,Jordi Bruix +23 more
TL;DR: In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo.
Journal ArticleDOI
The Protein Kinase Complement of the Human Genome
TL;DR: The protein kinase complement of the human genome is catalogued using public and proprietary genomic, complementary DNA, and expressed sequence tag sequences to provide a starting point for comprehensive analysis of protein phosphorylation in normal and disease states and a detailed view of the current state of human genome analysis through a focus on one large gene family.
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Sorafenib in advanced clear-cell renal-cell carcinoma.
Bernard Escudier,Tim Eisen,Walter M. Stadler,Cezary Szczylik,Stéphane Oudard,Michael Siebels,Sylvie Negrier,Christine Chevreau,Ewa Solska,Apurva A. Desai,Frederic Rolland,Tomasz Demkow,Thomas E. Hutson,Martin Gore,Scott Freeman,Brian Schwartz,M. Shan,Ronit Simantov,Ronald M. Bukowski +18 more
TL;DR: As compared with placebo, treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed; however, treatment is associated with increased toxic effects.
Journal ArticleDOI
BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF/MEK/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis
Scott Wilhelm,Christopher A. Carter,LiYa Tang,Dean Wilkie,Angela McNabola,Hong Rong,Charles Chen,Xiaomei Zhang,Patrick Vincent,Mark McHugh,Yichen Cao,Jaleel Shujath,Susan Gawlak,Deepa Eveleigh,Bruce Rowley,Li Liu,Lila Adnane,Mark Lynch,Daniel Auclair,Ian W. Taylor,Rich Gedrich,Andrei Voznesensky,Bernd Riedl,Leonard Post,Gideon Bollag,Pamela A. Trail +25 more
TL;DR: Data demonstrate that BAY 43-9006 is a novel dual action RAF kinase and VEGFR inhibitor that targets tumor cell proliferation and tumor angiogenesis.
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Mechanism of Activation of the Raf-Erk Signaling Pathway by Oncogenic Mutations of B-Raf
Paul T C Wan,Mathew J. Garnett,S. Mark Roe,Sharlene Lee,Dan Niculescu-Duvaz,Valerie M. Good,Cancer Genome,C. Michael Jones,Christopher J. Marshall,Caroline J. Springer,David Barford,Richard Marais +11 more
TL;DR: The high activity mutants signal to ERK by directly phosphorylating MEK, whereas the impaired activity mutants stimulate MEK by activating endogenous C-RAF, possibly via an allosteric or transphosphorylation mechanism.
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