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CuRE brAin TumOR Zurich (CREATORZ)

CREATORZ aims at changing the outcome for patients (of any age) with primary brain tumors by developing novel treatments, based on advanced imaging to guide precision medicine, molecular and functional profiling to dissect novel therapeutic opportunities, disease modeling to test new therapeutic approaches, and clinical translation using innovative trial designs.


Project Overview

Keywords

Brain, Glioma, Tumor

Background

Primary brain tumors affect approximately 20 individuals per 100,000 people annually worldwide. Some brain tumors such as glioblastoma are highly malignant and associated with poor outcome. Importantly, primary brain tumors are the major cause of cancer-associated mortality in children. Although profound advances in the understanding of molecular pathways resulting in brain tumor formation have been made in recent years, resulting in major changes to the WHO classification of brain tumors, these advances have not yet led to according improvements in the clinical management and better outcome for patients.

Key Objectives

The key objective of this interdisciplinary research program is to develop a multimodality research approach to understand across age groups why active treatments eventually fail and to develop novel treatment approaches for brain tumor patients for whom there are at present very few if any systemic treatment options beyond surgery and radiotherapy.

Methods

The applicants have established and will employ a broad spectrum of methods that will allow the successful conduct of the research plan: advanced neuroimaging and artificial intelligence-based image analysis (radiomics) (Work package WP1), next generation sequencing, proteomics, single cell immune cell profiling, and pharmacoscopy (WP2), novel genetic and pharmacological screening tools and in vivo models for common and rare brain tumors (WP3), innovative clinical trial designs including phase 0 (WP4), and integrative biostatistical analysis (WPZ).

Translation

Understanding patterns and mechanisms of acquired treatment resistance at the neuroimaging and molecular level (WP1, WP2) shall result in novel strategies of current treatment paradigms including neurosurgical approaches, radiotherapy and pharmacotherapy. Selective cancer cell vulnerabilities (WP2) can be confirmed and further mechanistically explored in relevant in vitro and in vivo models (WP3) and translated into early innovative clinical trial designs (WP4).

Medical Relevance

Brain tumors are an area of urgent medical need where there has been much less progress than in other areas of oncology. They are associated with particular high disease burden and cause major societal and economic loss.

Graphical Abstract 

Principal Investigators and cooperating departments

Martin Baumgartner, University Children’s Hospital Zurich, Children’s Research Center, Pediatric Molecular Neuro-Oncology Research, Balgrist Campus, Lengghalde 5, CH-8008 Zurich
Martin.Baumgartner@kispi.uzh.ch

Burkhard Becher, Institute of Experimental Immunology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich
becher@immunology.uzh.ch

Andrea Bink, Department of Neuroradiology, University Hospital Zurich, Frauenklinikstrasse 10, 8091 Zurich
andrea.bink@usz.ch

Jorn Fierstra, Department of Neurosurgery, University Hospital Zurich, Frauenklinikstrasse 10, 8091, Zurich
Jorn.fierstra@usz.ch

Michael Grotzer, Neuro-Oncology, University Children‘s Hospital of Zurich, Steinwiesstrasse 75, 8032 Zurich
Michael.Grotzer@kispi.uzh.ch

Matthias Guckenberger, Department of Radiation Oncology, University Hospital and University of Zurich, Rämistrasse 100, 8091 Zurich
Matthias.Guckenberger@usz.ch

Ana Guerreiro Stücklin, University Children’s Hospital Zurich and University of Zurich, Steinwiesstrasse 75, 8032 Zurich
Ana.Stuecklin@kispi.uzh.ch

Martin Huellner, Department of Nuclear Medicine, University Hospital Zurich / University of Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
Martin.huellner@usz.ch

Andras Jakab, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich
Andras.jakab@kispi.uzh.ch

Emilie Le Rhun, Department of Neurosurgery, and Brain Tumor Center, Comprehensive Cancer Center, University Hospital Zurich, Frauenklinikstrasse 10, 8091 Zurich
Emilie.lerhun@usz.ch

Michael Krauthammer, Department of Quantitative Biomedicine, University of Zurich, Schmelzbergstrasse 26, 8006 Zurich
Michael.Krauthammer@usz.ch

Björn Menze, Department of Quantitative Biomedicine, University of Zurich, Schmelzbergstrasse 26, 8006 Zurich
bjoern.menze@uzh.ch

Niklaus Krayenbühl, University Children‘s Hospital of Zurich, Steinwiesstrasse 75, 8032 Zurich
Niklaus.Krayenbuehl@kispi.uzh.ch

Holger Moch, Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Schmelzbergstrasse 12, 8091 Zurich
holger.moch@usz.ch

Sabine Müller, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich
sabine.mueller@kispi.uzh.ch

Javad Nazarian, Department of Oncology, University Children’s Hospital Zurich, Lengghalde 5, 8008 Zurich
Javad.Nazarian@kispi.uzh.ch

Luca Regli, Department of Neurosurgery, Brain Tumor Center, and Comprehensive Cancer Center, University Hospital and University of Zurich, Frauenklinikstrasse 10, 8091 Zurich
Luca.regli@usz.ch

Patrick Roth, Department of Neurology, University Hospital and University of Zurich, Frauenklinikstrasse 26, 8091 Zurich
patrick.roth@usz.ch

Gerald Schwank, Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich
gerald.schwank@uzh.ch

Manuela Silginer, Laboratory for Molecular Neuro-Oncology, Department of Neurology, University Hospital and University of Zurich, Frauenklinikstrasse 26, 8091 Zurich
manuela.silginer@usz.ch

Berend Snijder, Institute of Molecular Systems Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zurich
berend.snijder@imsb.biol.ethz.ch

Stephanie Tanadini-Lang, Department of Radiation Oncology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich
Stephanie.Tanadini-Lang@usz.ch

Flavio Vasella, Department of Neurosurgery, University Hospital Zurich, Frauenklinikstrasse 10, 8091, Zurich
flavio.vasella@usz.ch

Julia Velz, Department of Pediatric Neurosurgery, University Children’s Hospital Zurich, University of Zurich, Steinwiesstrasse 75, 8032 Zurich, and Department of Neurosurgery, University Hospital and University of Zurich, Frauenklinikstrasse 10, 8091 Zurich
julia.velz@usz.ch

Michael Weller, Department of Neurology, and Chairman, Brain Tumor Center, Comprehensive Cancer Center, University Hospital and University of Zurich, Frauenklinikstrasse 26, 8091 Zurich
Michael.weller@usz.ch

Tobias Weiss, Department of Neurology, University Hospital and University of Zurich, Frauenklinikstrasse 26, 8091 Zurich
tobias.weiss@usz.ch

Andreas Wicki, Department of Medical Oncology and Hematology, and Comprehensive Cancer Center, University Hospital and University of Zurich, Rämistrasse 100, 8091 Zurich
Andreas.Wicki@usz.ch

Hans-Georg Wirsching, Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich
hans-georg.wirsching@usz.ch

Contact

Michael Weller

Department of Neurology, USZ

Frauenklinikstrasse 26

8091 Zurich

Michael.Weller@usz.ch