List of communications


Targeting the transforming growth factor-β pathway in glioblastoma

Hannah Schneider, Laboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital Zurich, Zurich, Switzerland; Davide Mangani, Laboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital Zurich, Zurich, Switzerland; Emad Seyed Sadr, Laboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital Zurich, Zurich, Switzerland; Katharina Seystahl, Laboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital Zurich, Zurich, Switzerland; Ghazaleh Tabatabai, Interdisciplinary Division of Neuro-Oncology, Laboratory of Clinical and Experimental Neuro-Oncology, Hertie Institute for Clinical Brain Research, Eberhard Karls University, Tübingen, Germany; Edith Willscher, Interdisciplinary Centre for Bioinformatics, University of Leipzig, Leipzig, Germany; Hans Binder, Interdisciplinary Centre for Bioinformatics, University of Leipzig, Leipzig, Germany; Guido Reifenberger, Institute of Neuropathology, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany; Michael Weller, Laboratory of Molecular Neuro-Oncology, Department of Neurology, University Hospital Zurich, Zurich, Switzerland, Center for Neuroscience, University of Zurich, Zurich, Switzerland.


Transforming growth factor-β (TGF-β) is a master molecule that regulates, through the canonical and non-canonical arms of the signaling pathway, cell phenotypical changes that in gliomas have been linked with immunosuppression, invasiveness, angiogenesis and poor overall survival. Here we explored whether targeting this pathway provides tumor control in syngeneic mouse glioma models: SMA-497, SMA-540, SMA-560 in VM/Dk mice and GL-261 in C57BL/6 mice. Single agent activity was demonstrated for the TGF-β receptor I antagonist LY2157299 in SMA-540 and SMA-560. Reduction of pSMAD2 levels by LY2157299 was seen in all models, but did not predict response. Transcriptomic profiling delineated SMA-497 as the most angiogenic and SMA-497 and GL-261 as the most immunogenic tumors suggesting activity of potential pathways of primary or acquired resistance.

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