Title |
Kinase inhibitors can produce off-target effects and activate linked pathways by retroactivity
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Published in |
BMC Systems Biology, October 2011
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DOI | 10.1186/1752-0509-5-156 |
Pubmed ID | |
Authors |
Michelle L Wynn, Alejandra C Ventura, Jacques A Sepulchre, Héctor J García, Sofia D Merajver |
Abstract |
It has been shown in experimental and theoretical work that covalently modified signaling cascades naturally exhibit bidirectional signal propagation via a phenomenon known as retroactivity. An important consequence of retroactivity, which arises due to enzyme sequestration in covalently modified signaling cascades, is that a downstream perturbation can produce a response in a component upstream of the perturbation without the need for explicit feedback connections. Retroactivity may, therefore, play an important role in the cellular response to a targeted therapy. Kinase inhibitors are a class of targeted therapies designed to interfere with a specific kinase molecule in a dysregulated signaling pathway. While extremely promising as anti-cancer agents, kinase inhibitors may produce undesirable off-target effects by non-specific interactions or pathway cross-talk. We hypothesize that targeted therapies such as kinase inhibitors can produce off-target effects as a consequence of retroactivity alone. |
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Demographic breakdown
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Scientists | 1 | 50% |
Mendeley readers
Geographical breakdown
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United Kingdom | 1 | 1% |
France | 1 | 1% |
Russia | 1 | 1% |
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Researcher | 11 | 14% |
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Other | 4 | 5% |
Student > Master | 4 | 5% |
Other | 10 | 13% |
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Mathematics | 3 | 4% |
Other | 11 | 14% |
Unknown | 15 | 20% |