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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TL;DR: Since the publication of the American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) in 2005, new information has emerged that requires that the guidelines be updated.
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Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001-2011).
Jiang Wang,María Sánchez-Roselló,José Luis Aceña,Carlos del Pozo,Alexander E. Sorochinsky,Alexander E. Sorochinsky,Alexander E. Sorochinsky,Santos Fustero,Vadim A. Soloshonok,Vadim A. Soloshonok,Hong Liu +10 more
TL;DR: Introduced to the Market in the Last Decade (2001−2011) Jiang Wang,† María Sańchez-Rosello,́‡,§ Jose ́ Luis Aceña, Carlos del Pozo,‡ and Hong Liu.
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Josep M. Llovet,Michel Ducreux,Riccardo Lencioni,Adrian M. Di Bisceglie,Jean-Francois J. DuFour,Tim F. Greten,Eric Raymond,Tania Roskams,Vincenzo Mazzaferro,Jordi Bruix,Massimo Colombo,Andrew X. Zhu +11 more
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
Scott J. Dixon,Darpan N Patel,Matthew Welsch,Rachid Skouta,Eric D Lee,Miki Hayano,Ajit G. Thomas,Caroline E Gleason,Nicholas P. Tatonetti,Barbara S. Slusher,Brent R. Stockwell +10 more
TL;DR: Dixon, Patel, et al. as mentioned in this paper found that erastin is a very effective inhibitor of system xc− function and that it is over 1000 times more potent than the previously known best inhibitor, sulfasalazine.
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Molecular therapies and precision medicine for hepatocellular carcinoma
TL;DR: Treatment advances have been made in the past few years, and further advancements are expected in the near future, including biomarker-driven treatments and immunotherapies, as discussed in this Review.
References
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Journal ArticleDOI
Sorafenib Inhibits Imatinib-Resistant KIT and Platelet-Derived Growth Factor Receptor β Gatekeeper Mutants
Teresa Guida,Suresh Anaganti,Livia Provitera,Richard W. Gedrich,Elizabeth H. Sullivan,Scott Wilhelm,Massimo Santoro,Francesca Carlomagno +7 more
TL;DR: Sorafenib might be a promising anticancer agent for patients carrying KIT and PDGFRβ gatekeeper mutations, as well as activation of AP1-responsive and cyclin D1 gene promoters, respectively.
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Updated results of a randomized phase II study comparing two schedules of temozolomide in combination with sorafenib in patients with advanced melanoma
Ravi K. Amaravadi,Lynn M. Schuchter,D. F. McDermott,Amy Kramer,Lydia Giles,Andrea B. Troxel,C. A. Medina,K. L. Nathanson,Peter O'Dwyer,Keith T. Flaherty +9 more
TL;DR: This phase II trial testing sorafenib, an oral Raf kinase/VEGFR2 inhibitor, and temozolomide in pt with metastatic melanoma and prior TEM is to determine the optimal dosing of TEM, response, and toxicity rates.
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Increase of Renal Cell Carcinoma Incidence in Central Europe
Heiko Wunderlich,S. Schumann,V. Jantitzky,Petr Morávek,M. Podhola,Hartwig Kosmehl,Jörg Schubert +6 more
TL;DR: The percentage of clinically recognized RCCs in the total of all found R CCs in autopsies is nearly constant over the 11-year period in Jena and 10- year period in Hradec Králové, suggesting that the increased number of radical nephrectomies is not only caused by widespread use of ultrasonography.
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Medullary thyroid cancer: targeting the RET kinase pathway with sorafenib/tipifarnib
David S. Hong,Lei Ye,Robert F. Gagel,Lakshmi Chintala,Adel K. El Naggar,John J. Wright,Razelle Kurzrock +6 more
TL;DR: A rapid response to a sorafenib (RET and RAF kinase and vascular endothelial growth factor receptor inhibitor)–based regimen is reported in a patient with sporadic MTC who had advanced, progressive disease and a novel RET kinase aberration at exon 11 shown in tumor tissue.
Journal ArticleDOI
Comparison of antitumor effects of multitargeted tyrosine kinase inhibitors in acute myelogenous leukemia
Shuiying Hu,Hongmei Niu,Patton Minkin,Shelley Orwick,Akira Shimada,Hiroto Inaba,Gary V. Dahl,Jeffrey E. Rubnitz,Sharyn D. Baker +8 more
TL;DR: The results highlight the pharmacologic features of sorafenib that may provide it an advantage in the treatment of AML and that unbound sorafinib concentrations with activity against most AML cell lines are achievable in vivo.
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