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Dynamics and Sensitivity of Signaling Pathways

Abstract

Purpose of Review

Signaling pathways serve to communicate information about extracellular conditions into the cell, to both the nucleus and cytoplasmic processes to control cell responses. Genetic mutations in signaling network components are frequently associated with cancer and can result in cells acquiring an ability to divide and grow uncontrollably. Because signaling pathways play such a significant role in cancer initiation and advancement, their constituent proteins are attractive therapeutic targets. In this review, we discuss how signaling pathway modeling can assist with identifying effective drugs for treating diseases, such as cancer. An achievement that would facilitate the use of such models is their ability to identify controlling biochemical parameters in signaling pathways, such as molecular abundances and chemical reaction rates, because this would help determine effective points of attack by therapeutics.

Recent Findings

We summarize the current state of understanding the sensitivity of phosphorylation cycles with and without sequestration. We also describe some basic properties of regulatory motifs including feedback and feedforward regulation.

Summary

Although much recent work has focused on understanding the dynamics and particularly the sensitivity of signaling networks in eukaryotic systems, there is still an urgent need to build more scalable models of signaling networks that can appropriately represent their complexity across different cell types and tumors.

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Code Availability

Code for generating Fig. 1 is available at  https://github.com/sys-bio/CodeForPublishedPapers/tree/main/CurrentPathobiologyReports2021.

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Funding

This work was supported by National Cancer Institute under grant number U01CA242992. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, or the University of Washington.

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Correspondence to Michael A. Kochen.

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Kochen, M.A., Andrews, S.S., Wiley, H.S. et al. Dynamics and Sensitivity of Signaling Pathways. Curr Pathobiol Rep 10, 11–22 (2022). https://doi.org/10.1007/s40139-022-00230-y

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Keywords

  • Dynamics
  • Sensitivity
  • Signaling networks
  • Cancer