Neuro-oncology

Content

 


 

Introduction

The Laboratory of Molecular Neurooncology is located at the Department of Neurology of the University Hospital of Zurich (Frauenklinikstrasse 26). The Laboratory is led by Prof. Dr. M. Weller together with Dr. H. Schneider. PD Dr. P. Roth and Dr. Dr. I. Burghardt are group leaders supervising PhD students of the group (organisation chart). The networking within the NCCR and the Neuroscience Center Zurich has facilitated the development of several cooperations in Zurich.

Major research areas of the laboratory include cancer stem cell research, cancer immunology, angiogenesis, mechanisms of invasion and migration, and resistance to radiotherapy and chemotherapy.

Major goals of our research on cancer immunology include the characterization of immunological characteristics of glioma cells and tumor stem cells. We are focusing on "transforming growth factor" (TGF-beta)-mediated pathways and TGF-beta-targeting therapeutics. We further aim at establishing a preclinical model for an immunotoxin-based therapy in glioblastoma. In the framework of clinical trials, we seek to develop translational research concepts regarding the immunogenicity of glioma cells. In this context, we aim at understanding molecular mechanisms and risks of vaccination concepts in glioma and the immunogenicity of glioma cells and tumor stem cells.

We are further interested in mechanisms of resistance to anti-angiogenic therapies which target the vascular endothelial growth factor (VEGF pathway). Another major area of research focusses on integrins and c-Met as potential therapeutic targets and mediators of invasion and migration. In addition, we perform extensive studies on the primary and acquired resistance against the alkylating agent temozolomide with a specific focus on the role microRNAs.In cooperation with the Department of Neurosurgery (Prof. Dr. L. Regli), we currently establish a tumor bank collecting tumor tissue for histology and molecular analyses as well as for the isolation and characterization of tumor-derived glioma stem cells.

Methods employed include fluorescence tomography for in vivo imaging in our preclinical models, flow cytometry and in the framework of cooperations two-photon microscopy and positron emission tomography.

In the area of clinical neurooncology, we founded, together with the partner institutions of neuroradiology, neurosurgery, nuclear medicine, neuropathology, radiation oncology, medical oncology and pediatric neurooncology, the Brain Tumor Center Zurich at the Cancer Center Zurich in January 2012.

In cooperation with the Centers of the German Glioma Network and the German Consortium for Translational Cancer Research (DKTK), we are involved in several clinical pathological molecular correlative projects looking at, e.g. prognostic and predictive value of molecular markers such as 1p 19q codeletion, MGMT promotor methylation and isocytrate dehydrogenase mutations in different glioma entities and long-time survivors in glioblastoma (www.gliomnetzwerk.de).

The laboratory is supported by the Neuroscience Center Zurich (ZNZ), Swiss National Science Foundation, Oncosuisse, the Zurich Cancer League, the Wilhelm Sander-Foundation, the EMDO-Foundation, the Hartmann-Müller Foundation and the Koetser Foundation and performs cooperative research projects with the pharmaceutical companies 4SC (Martinsried, Germany), Alpinia Laudanum "Institute of Phytopharmaceutical Sciences" (Walenstadt), Antisense Pharma (Regensburg, Germany), Bayer (Leverkusen/Berlin, Deutschland), Celldex (Philipsburg, NJ, USA), Merck Serono (Darmstadt, Germany), Novocure (Jersey Isle), and Roche (Basel, Switzerland).

Address 

Department of Neurology and Laboratory for Molecular Neuro-Oncology
University Hospital Zurich
Frauenklinikstrasse 26
8091 Zurich
Switzerland

 

Team

Please click here to see the structural organisation chart.

You will find the list of group members on the following page.

Please click here to see the organisation chart of the laboratory teams.

 

Scientific projects

Selected scientific projects are listed in the table below. A complete overview and description of current and completed projects are listed on the website of the "Forschungsdatenbank" of the University of Zurich.  

 

Current scientific projects 

Funding source
Applicants
Titel
Duration
​Swiss National Science Foundation (SNF)
​M. Weller
H. Schneider
​Interferon typ I-based immunotherapy targeting glioma stem cells​04/2016-03/2019
Swiss National Science Foundation  and Sinergia
M. Weller
R. Roth
Focused ultrasound-mediated delivery of encapsulated MGMT antagonists for the treatment of temozolomide-resistant glioblastoma01/2014-12/2016
Swiss National Science Foundation
​P. Roth​Defining novel targets for chimeric antigen receptor (CAR)-based immunotherapy against glioblastoma​03/2017 - 02/2020
Oncosuisse / Swiss Cancer League
P. Roth
M. Weller
Integration of classical cancer therapy into novel concepts of immunotherapy for glioblastoma03/2015 - 02/2018
Oncosuisse / Swiss Cancer League
​M. Weller
H. Schneider
​Death induced by CD95 or CD95 ligand elimination (DICE) in glioblastoma​07/2016-06/2019
EMDO Foundation and SWFP. RothActivity of novel HDAC inhibitors against experimental gliomas07/2014-06/2015 resp. 2017 (SWF)
​Betty and David Koetser Foundation​D. Gramatzki​A population-based study on incidence, survival and molecular genetics of gliomas in the Canton of Zurich, Switzerland: a retrospective study from 2010-2014​01/2017-12/2017
​Foundation "Jubiläumsstiftung" Swiss Life
​H. Schneider
H.-G. Wirsching
​Neurobiology of glioblastoma stem cells and the role of mGlu3​07/2016-12/2017
Novartis Foundation
H.-G. Wirsching
M. Weller
​Thymosin-beta-4-dependent modulation of metabolic responses in glioma-initiating cells​07/2015-06/2017
Brain Tumor Funders' Collaborative
M. Weller
C. Hertler
Molecular genetic, host-derived and clinical determinants of long-term survival in glioblastoma01/2015-12/2016

 

 

Current clinical trials

Title
Principal Investi­gator
Indication
Contact in Zurich
Status
CheckMate 498, phase III

Nivolumab versus temozolomide, given with radiation therapy, for newly-diagnosed patients with glioblastoma
​Bristol-Myers Squibb,
PD Dr. P. Roth
​Newly diagnosed glioblastoma, unmethylated MGMT promotor​PD Dr. P. Roth
completed
CheckMate 548, phase III

Study of temozolomide plus radiation therapy with nivolumab or placebo, for newly diagnosed patients with glioblastoma
​Bristol-Myers Squibb,
PD Dr. P. Roth
​Newly diagnosed glioblastoma, methylated MGMT promotor​PD Dr. P. Rothrecruiting
STING: phase III

Randomized, double-blind, controlled study of ICT-107 in glioblastoma
​Prof. Dr. M. Weller,
Zürich
​Newly diagnosed glioblastoma​Prof. Dr. M. Weller​recruiting
MRZ-112: phase Ib

Multicenter, open-label study of marizomib combined with temozolomide and radiotherapy in patients with newly diagnosed  WHO Grade IV malignant glioma.
​PD Dr. P. Roth
​Newly diagnosed glioblastoma​PD Dr. P. Roth
​recruiting
PQR309-004, phase II

Open-label, non-randomized, two-stage study to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamic effects of PQR309 in patients with progressive glioblastoma
​Prof. Dr. M. Weller,
Zürich
​Recurrent glioblastoma
​Prof. Dr. M. Weller
Dr. D. Gramatzki
recruiting paused
M13-813, phase IIb/III

Temozolomide plus radiotherapy with ABT-414 or placebo, for newly diagnosed patients with glioblastoma
​AbbVie,
Dr. Lassman, New York
​Newly diagnosed glioblastoma with EGFR amplification
​Prof. Dr. M. Weller
Dr. C. Hertler
Dr. K. Seystahl
​recruiting
M14-483, EORTC 1410, phase II

ABT 414 or ABT 414 plus temozolomide versus lomustine oder temozolomide in patients with recurrent glioblastoma
​Prof. Dr. M. van den Bent, Rotterdam​Recurrent glioblastoma
​Prof. Dr. M. Weller,
Dr. C. Hertler
completed
BGJ398X2201, phase II

A multicenter, open-label study of BGJ398 in patients with recurrent resectable or unresectable glioblastoma
Novartis,
PD Dr. P. Roth
Recurrent glioblastoma with translocation of amplification of FGFR
PD Dr. P. Roth
Dr. C. Hertler
Dr. D. Gramatzki
completed
CheckMate 143, phase III

Open label study of nivolumab versus bevacizumab and a safety study of nivolumab or nivolumab in combination with ipilimumab in adult subjects with recurrent glioblastoma
Bristol-Myers Squibb,
PD Dr. P. Roth
Recurrent glioblastomaPD Dr. P. Rothcompleted
EORTC 1320, phase II

Trabectedin versus local standard of care therapy  for recurrent grade II or III meningioma
​Prof. Dr. M. Preusser, Wien​Recurrent meningeoma WHO grade II or III, no option for local treatment (surgery/radiation) ​PD Dr. P. Roth​recruiting
PQR309-005, phase II

Open-label, non-randomized, two-stage study to evaluate the efficacy and safety of PQR309 in patients with progressive primary CNS lymphoms
​Prof. Dr. M. Weller,
Zürich
​Recurrent primary CNS lymphoma
​Prof. Dr. M. Weller
Dr. D. Gramatzki
recruiting

 

 

Publications

Please follow the link to the detailed list of publications here.


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