Hutchinson2016 - Vascular phenotype identification and anti-angiogenic treatment recommendation

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Model Identifier
MODEL1911130007
Short description
This is a spatially averaged multiscale mathematical model of tumor angiogenesis. The model describes the dynamics of VEGF, Ang1, Ang2, and PDGF, coupled with those of mature and immature endothelial cells and pericyte cells.
Format
SBML (L2V4)
Related Publication
  • Vascular phenotype identification and anti-angiogenic treatment recommendation: A pseudo-multiscale mathematical model of angiogenesis.
  • Hutchinson LG, Gaffney EA, Maini PK, Wagg J, Phipps A, Byrne HM
  • Journal of theoretical biology , 6/ 2016 , Volume 398 , pages: 162-180 , PubMed ID: 26987523
  • Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Andrew Wiles Building, Radcliffe Observatory Quarter, Woodstock Road, Oxford OX2 6GG, UK. Electronic address: hutchinson@maths.ox.ac.uk.
  • The development of anti-angiogenic drugs for cancer therapy has yielded some promising candidates, but novel approaches for interventions to angiogenesis have led to disappointing results. In addition, there is a shortage of biomarkers that are predictive of response to anti-angiogenic treatments. Consequently, the complex biochemical and physiological basis for tumour angiogenesis remains incompletely understood. We have adopted a mathematical approach to address these issues, formulating a spatially averaged multiscale model that couples the dynamics of VEGF, Ang1, Ang2 and PDGF, with those of mature and immature endothelial cells and pericyte cells. The model reproduces qualitative experimental results regarding pericyte coverage of vessels after treatment by anti-Ang2, anti-VEGF and combination anti-VEGF/anti-Ang2 antibodies. We used the steady state behaviours of the model to characterise angiogenic and non-angiogenic vascular phenotypes, and used mechanistic perturbations representing hypothetical anti-angiogenic treatments to generate testable hypotheses regarding transitions to non-angiogenic phenotypes that depend on the pre-treatment vascular phenotype. Additionally, we predicted a synergistic effect between anti-VEGF and anti-Ang2 treatments when applied to an immature pre-treatment vascular phenotype, but not when applied to a normalised angiogenic pre-treatment phenotype. Based on these findings, we conclude that changes in vascular phenotype are predicted to be useful as an experimental biomarker of response to treatment. Further, our analysis illustrates the potential value of non-spatial mathematical models for generating tractable predictions regarding the action of anti-angiogenic therapies.
Contributors
Submitter of the first revision: Johannes Meyer
Submitter of this revision: Johannes Meyer
Modellers: Johannes Meyer

Metadata information

hasTaxon (1 statement)
Taxonomy Homo sapiens

hasProperty (2 statements)
Mathematical Modelling Ontology Ordinary differential equation model
NCIt Tumor Angiogenesis


Curation status
Non-curated


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Model files

Hutchinson2016.xml SBML L2V4 Representation of Hutchinson2016 - Vascular phenotype identification and anti-angiogenic treatment recommendation 148.91 KB Preview | Download

Additional files

Hutchinson2016.cps COPASI file of Hutchinson2016 - Vascular phenotype identification and anti-angiogenic treatment recommendation 267.96 KB Preview | Download

  • Model originally submitted by : Johannes Meyer
  • Submitted: Nov 13, 2019 8:14:57 PM
  • Last Modified: Nov 13, 2019 8:14:57 PM
Revisions
  • Version: 1 public model Download this version
    • Submitted on: Nov 13, 2019 8:14:57 PM
    • Submitted by: Johannes Meyer
    • With comment: Import of Hutchinson2016 - Vascular phenotype identification and anti-angiogenic treatment recommendation