Journal
MATHEMATICAL MEDICINE AND BIOLOGY-A JOURNAL OF THE IMA
Volume 29, Issue 1, Pages 95-108Publisher
OXFORD UNIV PRESS
DOI: 10.1093/imammb/dqq023
Keywords
agent-based model; multiscale; non-small cell lung cancer; epidermal growth factor receptor; transforming growth factor beta; signalling pathway
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Funding
- National Institutes of Health [CA 113004]
- Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging
- Department of Radiology at Massachusetts General Hospital
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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.
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