MAPK kinase signalling dynamics regulate cell fate decisions and drug resistance

Title: MAPK kinase signalling dynamics regulate cell fate decisions and drug resistance
Authors: Rauch, NoraRukhlenko, Oleksii S.Kolch, WalterKholodenko, Boris N.
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Date: Dec-2016
Online since: 2017-12-08T16:02:05Z
Abstract: The RAS/RAF/MEK/MAPK kinase pathway has been extensively studied for more than 25 years, yet we continue to be puzzled by its intricate dynamic control and plasticity. Different spatiotemporal MAPK dynamics bring about distinct cell fate decisions in normal vs cancer cells and developing organisms. Recent modelling and experimental studies provided novel insights in the versatile MAPK dynamics concerted by a plethora of feedforward/feedback regulations and crosstalk on multiple timescales. Multiple cancer types and various developmental disorders arise from persistent alterations of the MAPK dynamics caused by RAS/RAF/MEK mutations. While a key role of the MAPK pathway in multiple diseases made the development of novel RAF/MEK inhibitors a hot topic of drug development, these drugs have unexpected side-effects and resistance inevitably occurs. We review how RAF dimerization conveys drug resistance and recent breakthroughs to overcome this resistance.
Funding Details: European Commission Horizon 2020
European Commission - Seventh Framework Programme (FP7)
Type of material: Review
Publisher: Elsevier
Journal: Current Opinion in Structural Biology
Volume: 41
Start page: 151
End page: 158
Keywords: MAPKCell fate decisionsKinase signalling dynamicDrug resistanceRAS/RAF/MEKRAF dimerizationDrug therapies
DOI: 10.1016/
Language: en
Status of Item: Peer reviewed
This item is made available under a Creative Commons License:
Appears in Collections:Conway Institute Research Collection
SBI Research Collection
Medicine Research Collection

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