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, Nora
Rukhlenko, Oleksii S.
Kolch, Walter
Kholodenko, Boris N.
Permanent link:
Date: Dec-2016
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
Keywords: MAPKCell fate decisionsKinase signalling dynamicDrug resistanceRAS/RAF/MEKRAF dimerizationDrug therapies
DOI: 10.1016/
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
SBI Research Collection
Medicine Research Collection

Show full item record

Citations 20

Last Week
Last month
checked on Aug 10, 2018

Google ScholarTM



This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.