The ability of cells in multicellular organisms to respond to signals in their environment is critical for their survival, development and differentiation. Once differentiated and occupying their functional niche, cells need to maintain phenotypic stability while responding to diverse extracellular perturbations and environmental signals (such as nutrients, temperature, cytokines and hormones) in a co-ordinated manner. To achieve these requirements, cells have evolved numerous intracellular signalling mechanisms that confer on them the ability to resist, respond and adapt to external changes. Although fundamental to normal biological processes, as is evident from their evolutionary conservation, such mechanisms also allow cancer cells to evade targeted therapies, a problem of immediate clinical importance. In the present article, we discuss the role of signalling plasticity in the context of the mechanisms underlying both intrinsic and acquired resistance to targeted cancer therapies. We then examine the emerging analytical techniques and theoretical paradigms that are contributing to a greater understanding of signalling on a global and untargeted scale. We conclude with a discussion on how integrative approaches to the study of cell signalling have been used, and could be used in the future, to advance our understanding of resistance mechanisms to therapies that target the kinase signalling network.
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August 2014
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Conference Article|
August 11 2014
Approaches for measuring signalling plasticity in the context of resistance to targeted cancer therapies
Edmund H. Wilkes;
Edmund H. Wilkes
*Integrative Cell Signalling and Proteomics, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, U.K.
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Pedro Casado;
Pedro Casado
*Integrative Cell Signalling and Proteomics, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, U.K.
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Pedro R. Cutillas
*Integrative Cell Signalling and Proteomics, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, U.K.
2To whom correspondence should be addressed (email[email protected]).
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Publisher: Portland Press Ltd
Received:
January 21 2014
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem Soc Trans (2014) 42 (4): 791–797.
Article history
Received:
January 21 2014
Citation
Edmund H. Wilkes, Pedro Casado, Pedro R. Cutillas; Approaches for measuring signalling plasticity in the context of resistance to targeted cancer therapies. Biochem Soc Trans 1 August 2014; 42 (4): 791–797. doi: https://doi.org/10.1042/BST20140029
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