title: Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights.
abstract: Gliomas are highly invasive brain tumours characterised by poor prognosis and limited response to therapy. There is an ongoing debate on the therapeutic potential of vaso-modulatory interventions against glioma invasion. Prominent vasculature-targeting therapies involve tumour blood vessel deterioration and normalisation. The former aims at tumour infarction and nutrient deprivation induced by blood vessel occlusion/collapse. In contrast, the therapeutic intention of normalising the abnormal tumour vasculature is to improve the efficacy of conventional treatment modalities. Although these strategies have shown therapeutic potential, it remains unclear why they both often fail to control glioma growth. To shed some light on this issue, we propose a mathematical model based on the migration/proliferation dichotomy of glioma cells in order to investigate why vaso-modulatory interventions have shown limited success in terms of tumour clearance. We found the existence of a critical cell proliferation/diffusion ratio that separates glioma responses to vaso-modulatory interventions into two distinct regimes. While for tumours, belonging to one regime, vascular modulations reduce the front speed and increase the infiltration width, for those in the other regime, the invasion speed increases and infiltration width decreases. We discuss how these in silico findings can be used to guide individualised vaso-modulatory approaches to improve treatment success rates.
authors.affiliation: Braunschweig Integrated Centre of Systems Biology and Helmholtz Center for Infectious Research, Braunschweig, Germany.|Center for Information Services and High Performance Computing, Technische Universität Dresden, Germany.
authors.forename: J C L
authors.initials: JC
authors.lastname: Alfonso
authors.affiliation: Department of Biostatistics, Faculty of Medicine, University of Oslo, Norway.|BigInsight, Centre for Research-based Innovation (SFI), Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Köhn-Luque
authors.affiliation: Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus.
authors.forename: T
authors.initials: T
authors.lastname: Stylianopoulos
authors.affiliation: Institute of Pathology, Medical School of Hannover, Germany.|Institute of Neuropathology, University Clinic Freiburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Feuerhake
authors.affiliation: Center for Information Services and High Performance Computing, Technische Universität Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Deutsch
authors.affiliation: Braunschweig Integrated Centre of Systems Biology and Helmholtz Center for Infectious Research, Braunschweig, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Hatzikirou
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D003198:Computer Simulation; D005910:Glioma / Q000097:blood* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006801:Humans; D008959:Models, Neurological; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology / Q000628:therapy