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TMOD−03 * Motility controls growth and progression patterns of glioblastoma multiforme

Abstract : PURPOSE:Glioblastomamultiforme(GBM)is amalignant braintumor with poor prognosis and highmorbidity due to its invasiveness. Hypoxia-drivenmotility (HM) and concentration-driven motility (CM) are two mechanisms of GBM invasion in the brain. The use of anti-angiogenic drugs has uncovered new progression patterns of GBM associated with significant differences in overall survival times. Here, we test the hypotheses that the types and rates of GBM motility predict its progression pattern and the patients’ survival times. METHODS:We applied a mathematical model of GBMgrowth and invasion in humans to simulate a clinical trial and study the effects of the rate and mechanism of motility on the patterns of progression and on survival times. RESULTS: The motility phenotype appears to determine the progression pattern as well as the survival time of a patient treated by anti-angiogenesis. Highly-dispersive tumors are associated with the longest survival times (p , 0.001) and with progression by Expanding FLAIR. Moderately-Dispersive tumors are associated with short survival times and with progression by Expanding FLAIR + Necrosis. Tumors withHMare associated with the shortest survival times and with progression by Expanding Necrosis. The survival times of the latter are similar to non-responders. This investigation also uncovered theHM-CM principle: the aggressive HM-dependent phenotype surfaces only when therate of CM is low in both untreated and bevacizumab-treated GBM.CONCLUSIONS: Finding that the motility phenotype is a fundamental property that controls progression and survival times, has biological, clinical and therapeutic implications.
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https://hal.inria.fr/hal-01243554
Contributor : Olivier Saut <>
Submitted on : Tuesday, December 15, 2015 - 10:14:11 AM
Last modification on : Thursday, June 11, 2020 - 3:19:53 AM

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Olivier Saut, Thierry Colin, Hassan Fathallah, Elizabeth Scribner. TMOD−03 * Motility controls growth and progression patterns of glioblastoma multiforme. Neuro-Oncology, Oxford University Press (OUP), 2015, ⟨10.1093/neuonc/nov237.03⟩. ⟨hal-01243554⟩

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