Recent clinical data with BRAF and MEK1/2 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 1/2] inhibitors have demonstrated the remarkable potential of targeting the RAF–MEK1/2–ERK1/2 signalling cascade for the treatment of certain cancers. Despite these advances, however, only a subset of patients respond to these agents in the first instance, and, of those that do, acquired resistance invariably develops after several months. Studies in vitro have identified various mechanisms that can underpin intrinsic and acquired resistance to MEK1/2 inhibitors, and these frequently recapitulate those observed clinically. In the present article, we review these mechanisms and also discuss recent advances in our understanding of how MEK1/2 inhibitor activity is influenced by pathway feedback.
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Conference Article|
August 11 2014
Intrinsic and acquired resistance to MEK1/2 inhibitors in cancer
Matthew J. Sale;
Matthew J. Sale
1
*Signalling Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, U.K.
1Correspondence may be addressed to either author (emailmatthew.sale@babraham.ac.uk or simon.cook@babraham.ac.uk).
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Simon J. Cook
Simon J. Cook
1
*Signalling Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, U.K.
1Correspondence may be addressed to either author (emailmatthew.sale@babraham.ac.uk or simon.cook@babraham.ac.uk).
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Publisher: Portland Press Ltd
Received:
May 01 2014
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem Soc Trans (2014) 42 (4): 776–783.
Article history
Received:
May 01 2014
Citation
Matthew J. Sale, Simon J. Cook; Intrinsic and acquired resistance to MEK1/2 inhibitors in cancer. Biochem Soc Trans 1 August 2014; 42 (4): 776–783. doi: https://doi.org/10.1042/BST20140129
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