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Effects of Anti-Angiogenesis on Glioblastoma Growth and Migration: Model to Clinical Predictions

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  • Elizabeth Scribner
  • Olivier Saut
  • Paula Province
  • Asim Bag
  • Thierry Colin
  • Hassan M Fathallah-Shaykh

Abstract

Glioblastoma multiforme (GBM) causes significant neurological morbidity and short survival times. Brain invasion by GBM is associated with poor prognosis. Recent clinical trials of bevacizumab in newly-diagnosed GBM found no beneficial effects on overall survival times; however, the baseline health-related quality of life and performance status were maintained longer in the bevacizumab group and the glucocorticoid requirement was lower. Here, we construct a clinical-scale model of GBM whose predictions uncover a new pattern of recurrence in 11/70 bevacizumab-treated patients. The findings support an exception to the Folkman hypothesis: GBM grows in the absence of angiogenesis by a cycle of proliferation and brain invasion that expands necrosis. Furthermore, necrosis is positively correlated with brain invasion in 26 newly-diagnosed GBM. The unintuitive results explain the unusual clinical effects of bevacizumab and suggest new hypotheses on the dynamic clinical effects of migration by active transport, a mechanism of hypoxia-driven brain invasion.

Suggested Citation

  • Elizabeth Scribner & Olivier Saut & Paula Province & Asim Bag & Thierry Colin & Hassan M Fathallah-Shaykh, 2014. "Effects of Anti-Angiogenesis on Glioblastoma Growth and Migration: Model to Clinical Predictions," PLOS ONE, Public Library of Science, vol. 9(12), pages 1-21, December.
    • Handle: RePEc:plo:pone00:0115018
    DOI: 10.1371/journal.pone.0115018
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