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Mol Cancer Ther. 2005 Apr;4(4):677-85.

Raf kinase as a target for anticancer therapeutics.

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1
Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, 610 University Avenue, Suite 5-210, Toronto, Ontario, Canada M5G 2M9.

Abstract

The Ras-Raf-MEK-ERK (ERK) pathway is a logical therapeutic target because it represents a common downstream pathway for several key growth factor tyrosine kinase receptors which are often mutated or overexpressed in human cancers. Although considered mainly growth-promoting, in certain contexts, this pathway also seems to be apoptosis-suppressing. Several novel agents targeting this pathway have now been developed and are in clinical trials. One of the most interesting new agents is BAY 43-9006. Although initially developed as a Raf kinase inhibitor, it can also target several other important tyrosine kinases including VEGFR-2, Flt-3, and c-Kit, which contributes to its antiproliferative and antiangiogenic properties. To date, encouraging results have been seen with BAY 43-9006, particularly in renal cell cancers which are highly vascular tumors. This review will provide an overview of the ERK signaling pathway in normal and neoplastic tissue, with a specific focus on novel therapies targeting the ERK pathway at the level of Raf kinase.

PMID:
15827342
DOI:
10.1158/1535-7163.MCT-04-0297
[Indexed for MEDLINE]
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