Journal Article

Identifying therapeutic targets in a combined EGFR–TGFβR signalling cascade using a multiscale agent-based cancer model

Zhihui Wang, Veronika Bordas, Jonathan Sagotsky and Thomas S. Deisboeck

in Mathematical Medicine and Biology: A Journal of the IMA

Published on behalf of Institute of Mathematics and its Applications

Volume 29, issue 1, pages 95-108
Published in print March 2012 | ISSN: 1477-8599
Published online December 2010 | e-ISSN: 1477-8602 | DOI: http://dx.doi.org/10.1093/imammb/dqq023
Identifying therapeutic targets in a combined EGFR–TGFβR signalling cascade using a multiscale agent-based cancer model

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Applying a previously developed non-small cell lung cancer model, we assess ‘cross-scale’ the therapeutic efficacy of targeting a variety of molecular components of the epidermal growth factor receptor (EGFR) signalling pathway. Simulation of therapeutic inhibition and amplification allows for the ranking of the implemented downstream EGFR signalling molecules according to their therapeutic values or indices. Analysis identifies mitogen-activated protein kinase and extracellular signal-regulated kinase as top therapeutic targets for both inhibition and amplification-based treatment regimen but indicates that combined parameter perturbations do not necessarily improve the therapeutic effect of the separate parameter treatments as much as might be expected. Potential future strategies using this in silico model to tailor molecular treatment regimen are discussed.

Keywords: agent-based model; multiscale; non-small cell lung cancer; epidermal growth factor receptor; transforming growth factor β; signalling pathway

Journal Article.  0 words. 

Subjects: Applied Mathematics ; Biomathematics and Statistics

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