期刊
MATHEMATICAL MEDICINE AND BIOLOGY-A JOURNAL OF THE IMA
卷 32, 期 3, 页码 239-262出版社
OXFORD UNIV PRESS
DOI: 10.1093/imammb/dqu002
关键词
glioblastoma multiforme; antithrombotic; radiotherapy; antioxidants; combined therapies
资金
- Ministerio de Economia y Competitividad, Spain [MTM2012-31073]
- James S. McDonnell Foundation (USA) through 21st Century Science Initiative in Mathematical & Complex Systems Approaches for Brain Cancer-Pilot Award [220020351]
Glioblastoma multiforme (GBM), the most frequent type of primary brain tumour, is a rapidly evolving and spatially heterogeneous high-grade astrocytoma that presents areas of necrosis, hypercellularity and microvascular hyperplasia. The aberrant vasculature leads to hypoxic areas and results in an increase in oxidative stress, selecting for more invasive tumour cell phenotypes. In our study, we assay in silico different therapeutic approaches which combine antithrombotics (ATs), antioxidants and standard radiotherapy (RT). To do so, we have developed a biocomputational model of GBM that incorporates the spatio-temporal interplay among two glioma cell phenotypes corresponding to oxygenated and hypoxic cells, a necrotic core and the local vasculature whose response evolves with tumour progression. Our numerical simulations predict that suitable combinations of ATs and antioxidants may diminish, in a synergistic way, oxidative stress and the subsequent hypoxic response. This novel therapeutical strategy, with potentially low or no toxicity, might reduce tumour invasion and further sensitize GBM to conventional RT or other cytotoxic agents, hopefully increasing median patient overall survival time.
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