Computational modelling of perivascular-niche dynamics for the optimization of treatment schedules for glioblastoma.
Nat Biomed Eng
; 5(4): 346-359, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33864039
ABSTRACT
Glioblastoma stem-like cells dynamically transition between a chemoradiation-resistant state and a chemoradiation-sensitive state. However, physical barriers in the tumour microenvironment restrict the delivery of chemotherapy to tumour compartments that are distant from blood vessels. Here, we show that a massively parallel computational model of the spatiotemporal dynamics of the perivascular niche that incorporates glioblastoma stem-like cells and differentiated tumour cells as well as relevant tissue-level phenomena can be used to optimize the administration schedules of concurrent radiation and temozolomide-the standard-of-care treatment for glioblastoma. In mice with platelet-derived growth factor (PDGF)-driven glioblastoma, the model-optimized treatment schedule increased the survival of the animals. For standard radiation fractionation in patients, the model predicts that chemotherapy may be optimally administered about one hour before radiation treatment. Computational models of the spatiotemporal dynamics of the tumour microenvironment could be used to predict tumour responses to a broader range of treatments and to optimize treatment regimens.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
/
Glioblastoma
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Antineoplásicos Alquilantes
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Temozolomida
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Modelos Biológicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Biomed Eng
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos