The complexities and versatility of the RAS-to-ERK signalling system in normal and cancer cells

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Title: The complexities and versatility of the RAS-to-ERK signalling system in normal and cancer cells
Authors: Fey, Dirk
Matallanas, David
Rauch, Jens
Rukhlenko, Oleksii S.
Kholodenko, Boris N.
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Date: Oct-2016
Online since: 2019-04-02T11:12:23Z
Abstract: The intricate dynamic control and plasticity of RAS to ERK mitogenic, survival and apoptotic signalling has mystified researches for more than 30 years. Therapeutics targeting the oncogenic aberrations within this pathway often yield unsatisfactory, even undesired results, as in the case of paradoxical ERK activation in response to RAF inhibition. A direct approach of inhibiting single oncogenic proteins misses the dynamic network context governing the network signal processing. In this review, we discuss the signalling behaviour of RAS and RAF proteins in normal and in cancer cells, and the emerging systems-level properties of the RAS-to-ERK signalling network. We argue that to understand the dynamic complexities of this control system, mathematical models including mechanistic detail are required. Looking into the future, these dynamic models will build the foundation upon which more effective, rational approaches to cancer therapy will be developed.
Funding Details: European Commission Horizon 2020
European Commission - Seventh Framework Programme (FP7)
Science Foundation Ireland
Type of material: Review
Publisher: Elsevier
Journal: Seminars in Cell & Developmental Biology
Volume: 58
Start page: 96
End page: 107
Copyright (published version): 2016 Elsevier
Keywords: Dynamic modellingMAPK cascadeSystems biology
DOI: 10.1016/j.semcdb.2016.06.011
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
SBI Research Collection
Medicine Research Collection

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