Computational modelling of perivascular-niche dynamics for the optimization of treatment schedules for glioblastoma.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Randles, A; Wirsching, H-G; Dean, JA; Cheng, Y-K; Emerson, S; Pattwell, SS; Holland, EC; Michor, F

Published Date

  • April 16, 2021

Published In

Volume / Issue

  • 5 / 4

Start / End Page

  • 346 - 359

PubMed ID

  • 33864039

Pubmed Central ID

  • PMC8054983

Electronic International Standard Serial Number (EISSN)

  • 2157-846X

International Standard Serial Number (ISSN)

  • 2157-846X

Digital Object Identifier (DOI)

  • 10.1038/s41551-021-00710-3

Language

  • eng