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

Complex Biosystems Modeling Laboratory, Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital-East, 13th Street, Charlestown, MA 02129, USA.
Mathematical Medicine and Biology (Impact Factor: 1.66). 12/2010; 29(1):95-108. DOI: 10.1093/imammb/dqq023
Source: PubMed


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.

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Available from: Zhihui Wang, Jan 16, 2015
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