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Targeting the Extracellular Signal-Regulated Kinase Pathway in Cancer Therapy


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Title: Targeting the Extracellular Signal-Regulated Kinase Pathway in Cancer Therapy
Authors: Kohno, Michiaki / Tanimura, Susumu / Ozaki, Kei-ichi
Issue Date: Dec-2011
Publisher: Pharmaceutical Society of Japan / 日本薬学会
Citation: Biological and Pharmaceutical Bulletin, 34(12), pp.1781-1784; 2011
Abstract: The extracellular signal-regulated kinase (ERK) pathway is a major determinant in the control of diverse cellular processes such as proliferation, survival, and motility. This pathway is often upregulated in human cancers and as such represents an attractive target for mechanism-based approaches to cancer treatment. However, specific blockade of the ERK pathway alone induces mostly cytostatic rather than proapoptotic effects, resulting in limited therapeutic efficacy. Blockade of the constitutively activated ERK pathway by an ERK kinase (MEK) inhibitor sensitizes tumor cells to apoptotic cell death induced by several cytotoxic anticancer agents including microtubule-destabilizing agents and histone deacetylase inhibitors, not only in vitro but also in tumor zenografts in vivo. Thus, low concentrations of these anticancer drugs that by themselves show little cytotoxicity effectively kill tumor cells in which the ERK pathway is constitutively activated when co-administrated with a MEK inhibitor. The combination of a cytostatic signaling pathway inhibitor (MEK inhibitors) and conventional anticancer drugs (microtubule-destabilizing agents or histone deacetylase inhibitors) provides an excellent basis for the development of safer anticancer chemotherapies with enhanced efficacy through lowering the required dose of the latter cytotoxic drugs.
Keywords: Anticancer drug / Combination therapy / ERK pathway / MEK inhibitor / Molecular targeted therapy
URI: http://hdl.handle.net/10069/27064
ISSN: 09186158
Rights: © 2011 Pharmaceutical Society of Japan.
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/27064

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