MEK in cancer and cancer therapy.

Details

Serval ID
serval:BIB_FBEEE2D7C1CB
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Title
MEK in cancer and cancer therapy.
Journal
Pharmacology and Therapeutics
Author(s)
Neuzillet C., Tijeras-Raballand A., de Mestier L., Cros J., Faivre S., Raymond E.
ISSN
1879-016X (Electronic)
ISSN-L
0163-7258
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
141
Number
2
Pages
160-171
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review Publication Status: ppublish
Abstract
The mitogen-activated extracellular signal-regulated kinase (MEK) pathway is one of the best-characterized kinase cascades in cancer cell biology. It is triggered by either growth factors or activating mutations of major oncogenic proteins in this pathway, the most common being Ras and Raf. Deregulation of this pathway is frequently observed and plays a central role in the carcinogenesis and maintenance of several cancers, including melanoma, pancreatic, lung, colorectal, and breast cancers. Targeting these kinases offers promise of novel therapies. MEK inhibitors (MEKi) are currently under evaluation in clinical trials and many have shown activity. In this review, we comprehensively examine the role of the MEK pathway in carcinogenesis and its therapeutic potential in cancer patients, with a focus on MEKi. We describe the clinical perspectives of MEKi in the two main models of Ras-ERK driven tumors, BRAF-mutant ("addicted" to the pathway) and KRAS-mutant (non-"addicted"). We also highlight the known mechanisms of resistance to MEKi and emerging strategies to overcome it.
Keywords
Animals, Antineoplastic Agents/therapeutic use, Drug Resistance, Neoplasm, Extracellular Signal-Regulated MAP Kinases/metabolism, Humans, MAP Kinase Kinase Kinases/antagonists & inhibitors, MAP Kinase Kinase Kinases/metabolism, Neoplasms/drug therapy, Neoplasms/genetics, Protein Kinase Inhibitors/therapeutic use, ras Proteins/metabolism
Pubmed
Create date
11/02/2015 12:01
Last modification date
20/08/2019 16:27
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