Over the last two decades, many small-molecule inhibitors that target kinase signalling have been developed. More than 20 of these inhibitors are FDA (U.S. Food and Drug Administration)-approved and are now being used in the clinics to treat tumours; even more have entered clinical trials. However, resistance to these inhibitors, either intrinsic to the tumour or acquired during treatment, remains a major problem in targeted therapeutics. One of the mechanisms by which tumours become resistant is the rewiring of the signalling networks via feedback, by which the tumour cells re-activate signalling or activate alternative signalling pathways. In the present article, we review insights from recent quantitative signalling studies combining mathematical modelling and experiments that revealed how feedback rewires MAPK (mitogen-activated protein kinase)/PI3K (phosphoinositide 3-kinase) signalling upon treatment and how that affects drug sensitivity.
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Conference Article|
August 11 2014
Consequences of feedback in signal transduction for targeted therapies Available to Purchase
Bertram Klinger;
Bertram Klinger
*Institute of Pathology, Charité–Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
†Integrative Research Institute (IRI) for the Life Sciences, Humboldt-Universität zu Berlin, Unter den Linden 6, 10099 Berlin, Germany
‡Institute for Theoretical Biology, Humboldt-Universität zu Berlin, Invalidenstrasse 43, 10115 Berlin, Germany
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Nils Blüthgen
Nils Blüthgen
1
*Institute of Pathology, Charité–Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
†Integrative Research Institute (IRI) for the Life Sciences, Humboldt-Universität zu Berlin, Unter den Linden 6, 10099 Berlin, Germany
‡Institute for Theoretical Biology, Humboldt-Universität zu Berlin, Invalidenstrasse 43, 10115 Berlin, Germany
1To whom correspondence should be addressed (email[email protected]).
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Publisher: Portland Press Ltd
Received:
May 07 2014
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem Soc Trans (2014) 42 (4): 770–775.
Article history
Received:
May 07 2014
Citation
Bertram Klinger, Nils Blüthgen; Consequences of feedback in signal transduction for targeted therapies. Biochem Soc Trans 1 August 2014; 42 (4): 770–775. doi: https://doi.org/10.1042/BST20140130
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