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Accession IconGSE114438

A PDGFR-driven mouse model of Glioblastoma reveals a Stathmin1-mediated mechanism of sensitivity to Vinblastine

Organism Icon Mus musculus
Sample Icon 9 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

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Glioblastoma multiforme (GBM) is an aggressive primary brain cancer that includes focal amplification of PDGFR and for which there are no effective therapies. Herein, we report the development of a genetically engineered mouse model of GBM based on autocrine, chronic stimulation of PDGFR and the analysis of GBM signaling pathways using proteomics. We discovered the tubulin-binding protein Stathmin1 (STMN1) as a PDGFR phospho-regulated target and that this mis-regulation conferred selective sensitivity to vinblastine (VB) cytotoxicity. Treatment of PDGFR GBMs with VB in mice drastically prolonged survival and was dependent on STMN1. Our work provides a rationale for evaluating genotype-specific anti-microtubule drugs as cancer treatment in select GBM patient populations.
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