IMR Press / FBL / Volume 15 / Issue 1 / DOI: 10.2741/3619

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
A pharmacodynamic model of Aurora kinase inhibitors in the spindle assembly checkpoint
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1 Division of Mathematics, University of Dundee, Dundee DD1 4HN, Scotland, UK
2 Cyclacel Ltd., James Lindsay Place, Dundee DD1 5JJ, Scotland, UK
Front. Biosci. (Landmark Ed) 2010, 15(1), 249–258; https://doi.org/10.2741/3619
Published: 1 January 2010
Abstract

Arguably the most dramatic phase in the cell cycle is mitosis, during which replicated chromosomes are sorted into two distinct sets. Aurora kinases are central to the accurate segregation of chromosomes during mitosis. Consequently, they have been selected as possible targets for cancer therapy. Anti-cancer drugs that target Aurora kinases are normally designed to inhibit their function. The complexity of the roles of Aurora kinases and their interaction with respective inhibitors means that it is often very difficult to obtain meaningful links between inhibitor concentration and efficacy using standard methods. To overcome these difficulties, we propose a novel mathematical modelling approach. We present a pharmacodynamic model that is able to encapsulate the key roles of two kinases, Aurora A and B, in the spindle assembly checkpoint. Moreover, the model is capable of qualitatively differentiating between the effects of inhibiting Aurora A, Aurora B and A plus B, respectively, by predicting cell behaviour. Consequently, predictions regarding the qualitative relationship between inhibitors, measurable biomarkers and cell damage can be obtained using this powerful modelling approach.

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