Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • J. C. L. Alfonso - , Biologische Algorithmen (FoG) (cfaed), Braunschweig Integrated Centre of Systems Biology (BRICS), Helmholtz-Zentrum für Infektionsforschung (HZI) (Autor:in)
  • Alvaro Köhn-Luque - , University of Oslo, BigInsight (Autor:in)
  • T Stylianopoulos - , University of Cyprus (Autor:in)
  • F. Feuerhake - , Medizinische Hochschule Hannover (MHH), Universitätsklinikum Freiburg (Autor:in)
  • Andreas Deutsch - , Zentrum für Informationsdienste und Hochleistungsrechnen (ZIH) (Autor:in)
  • Haralambos Hatzikirou - , Braunschweig Integrated Centre of Systems Biology (BRICS), Helmholtz-Zentrum für Infektionsforschung (HZI) (Autor:in)

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.

Details

OriginalspracheEnglisch
Aufsatznummer37283
Seitenumfang16
FachzeitschriftScientific Reports
Jahrgang6
PublikationsstatusVeröffentlicht - 2016
Peer-Review-StatusJa

Externe IDs

Scopus 84997132543
ORCID /0000-0002-1270-7885/work/211721172