title: Identifying therapeutic targets in a combined EGFR-TGFβR signalling cascade using a multiscale agent-based cancer model.
abstract: 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.
authors.affiliation: Complex Biosystems Modeling Laboratory, Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital-East, 13th Street, Charlestown, MA 02129, USA.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Wang
authors.forename: Veronika
authors.initials: V
authors.lastname: Bordas
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sagotsky
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Deisboeck
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism*; D003198:Computer Simulation; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D055641:Mathematical Concepts; D008954:Models, Biological; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D049490:Systems Biology; D059016:Tumor Microenvironment; D014584:User-Computer Interface
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D066246:ErbB Receptors