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MAPK kinase signalling dynamics regulate cell fate decisions and drug resistance
Date Issued
2016-12
Date Available
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.
Sponsorship
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
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
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MAPK kinase signalling dynamics regulate cell fate decisions & drug resistance KolchW, KholodenkoB TBC.pdf
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892.27 KB
Format
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68
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