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

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

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)95-108
Number of pages14
JournalMathematical Medicine and Biology
Volume29
Issue number1
DOIs
StatePublished - Mar 19 2012

Keywords

  • Agent-based model
  • Epidermal growth factor receptor
  • Multiscale
  • Non-small cell lung cancer
  • Signalling pathway
  • Transforming growth factor β

ASJC Scopus subject areas

  • Pharmacology
  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Environmental Science(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Modeling and Simulation
  • Applied Mathematics

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