A Mechanistic Investigation into Ischemia-Driven Distal Recurrence of Glioblastoma

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number143
JournalBulletin of Mathematical Biology
Volume82
Issue number11
DOIs
StatePublished - Nov 1 2020

Keywords

  • Glioblastoma
  • Hypoxia
  • Ischemia
  • PIHNA
  • Tumor growth

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Mathematics(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Pharmacology
  • Agricultural and Biological Sciences(all)
  • Computational Theory and Mathematics

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