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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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Alfonso JC,Köhn-Luque A,Stylianopoulos T,Feuerhake F,Deutsch A,Hatzikirou H

doi

10.1038/srep37283

subject

Has Abstract

pub_date

2016-11-23 00:00:00

pages

37283

issn

2045-2322

pii

srep37283

journal_volume

6

pub_type

杂志文章

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