A Mechanistic Investigation into Ischemia-Driven Distal Recurrence of Glioblastoma

Curtin, Lee; Hawkins-Daarud, Andrea; Porter, Alyx B.; van der Zee, Kristoffer G.; Owen, Markus R.; Swanson, Kristin R.

Abstract

Glioblastoma (GBM) is the most aggressive primary brain tumor with a short median survival. Tumor recurrence is a clinical expectation of this disease and usually occurs along the resection cavity wall. However, previous clinical observations have suggested that in cases of ischemia following surgery, tumors are more likely to recur distally. Through the use of a previously established mechanistic model of GBM, the Proliferation Invasion Hypoxia Necrosis Angiogenesis (PIHNA) model, we explore the phenotypic drivers of this observed behavior. We have extended the PIHNA model to include a new nutrient-based vascular efficiency term that encodes the ability of local vasculature to provide nutrients to the simulated tumor. The extended model suggests sensitivity to a hypoxic microenvironment and the inherent migration and proliferation rates of the tumor cells are key factors that drive distal recurrence.

• Journal Article Type: Article
• Acceptance Date: Sep 25, 2020
• Online Publication Date: Nov 7, 2020
• Publication Date: Nov 7, 2020
• Deposit Date: Dec 2, 2020
• Publicly Available Date: Nov 8, 2021
• Journal: Bulletin of Mathematical Biology
• Print ISSN: 0092-8240
• Electronic ISSN: 1522-9602
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 82
• Issue: 11
• Article Number: 143
• DOI: https://doi.org/10.1007/s11538-020-00814-y
• Keywords: Immunology; General Biochemistry, Genetics and Molecular Biology; Computational Theory and Mathematics; General Neuroscience; Pharmacology; General Agricultural and Biological Sciences; General Mathematics; General Environmental Science
• Public URL: https://nottingham-repository.worktribe.com/output/5040232
• Publisher URL: https://link.springer.com/article/10.1007/s11538-020-00814-y