MAPK kinase signalling dynamics regulate cell fate decisions and drug resistance
Files in This Item:
|MAPK kinase signalling dynamics regulate cell fate decisions & drug resistance KolchW, KholodenkoB TBC.pdf||892.27 kB||Adobe PDF||Download|
|Title:||MAPK kinase signalling dynamics regulate cell fate decisions and drug resistance||Authors:||Rauch, Nora
Rukhlenko, Oleksii S.
Kholodenko, Boris N.
|Permanent link:||http://hdl.handle.net/10197/9082||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:||MAPK; Cell fate decisions; Kinase signalling dynamic; Drug resistance; RAS/RAF/MEK; RAF dimerization; Drug therapies||DOI:||10.1016/j.sbi.2016.07.019||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Conway Institute Research Collection|
SBI Research Collection
Medicine Research Collection
Show full item record
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.