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.