title: Numerical simulation of vascular tumour growth under antiangiogenic treatment: addressing the paradigm of single-agent bevacizumab therapy with the use of experimental data.
abstract: BACKGROUND
  Antiangiogenic agents have been recently added to the oncological armamentarium with bevacizumab probably being the most popular representative in current clinical practice. The elucidation of the mode of action of these agents is a prerequisite for personalized prediction of antiangiogenic treatment response and selection of patients who may benefit from this kind of therapy. To this end, having used as a basis a preexisting continuous vascular tumour growth model which addresses the targeted nature of antiangiogenic treatment, we present a paper characterized by the following three features. First, the integration of a two-compartmental bevacizumab specific pharmacokinetic module into the core of the aforementioned preexisting model. Second, its mathematical modification in order to reproduce the asymptotic behaviour of tumour volume in the theoretical case of a total destruction of tumour neovasculature. Third, the exploitation of a range of published animal datasets pertaining to antitumour efficacy of bevacizumab on various tumour types (breast, lung, head and neck, colon).
  
  
  RESULTS
  Results for both the unperturbed growth and the treatment module reveal qualitative similarities with experimental observations establishing the biologically acceptable behaviour of the model. The dynamics of the untreated tumour has been studied via a parameter analysis, revealing the role of each relevant input parameter to tumour evolution. The combined effect of endogenous proangiogenic and antiangiogenic factors on the angiogenic potential of a tumour is also studied, in order to capture the dynamics of molecular competition between the two key-players of tumoural angiogenesis. The adopted methodology also allows accounting for the newly recognized direct antitumour effect of the specific agent.
  
  
  CONCLUSIONS
  Interesting observations have been made, suggesting a potential size-dependent tumour response to different treatment modalities and determining the relative timing of cytotoxic versus antiangiogenic agents administration. Insight into the comparative effectiveness of different antiangiogenic treatment strategies is revealed. The results of a series of in vivo experiments in mice bearing diverse types of tumours (breast, lung, head and neck, colon) and treated with bevacizumab are successfully reproduced, supporting thus the validity of the underlying model.
authors.affiliation: In Silico Oncology and In Silico Medicine Group, Laboratory of Microwaves and Fiber Optics, Institute of Communication and Computer Systems, School of Electrical and Computer Engineering, National Technical University of Athens, 9 Iroon Polytechniou, Zografos, GR 157 80, Athens, Greece.
authors.forename: Katerina D
authors.initials: KD
authors.lastname: Argyri
authors.affiliation: In Silico Oncology and In Silico Medicine Group, Laboratory of Microwaves and Fiber Optics, Institute of Communication and Computer Systems, School of Electrical and Computer Engineering, National Technical University of Athens, 9 Iroon Polytechniou, Zografos, GR 157 80, Athens, Greece.
authors.forename: Dimitra D
authors.initials: DD
authors.lastname: Dionysiou
authors.affiliation: In Silico Oncology and In Silico Medicine Group, Laboratory of Microwaves and Fiber Optics, Institute of Communication and Computer Systems, School of Electrical and Computer Engineering, National Technical University of Athens, 9 Iroon Polytechniou, Zografos, GR 157 80, Athens, Greece.
authors.forename: Fay D
authors.initials: FD
authors.lastname: Misichroni
authors.affiliation: In Silico Oncology and In Silico Medicine Group, Laboratory of Microwaves and Fiber Optics, Institute of Communication and Computer Systems, School of Electrical and Computer Engineering, National Technical University of Athens, 9 Iroon Polytechniou, Zografos, GR 157 80, Athens, Greece. gestam@central.ntua.gr.
authors.forename: Georgios S
authors.initials: GS
authors.lastname: Stamatakos
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000068258:Bevacizumab / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy
chemical_list: D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab
keywords: Antiangiogenic treatment; Computational oncology; Continuous model; Dynamical system; In silico oncology; Vascular tumour growth