Project Details
SFB 1389: Understanding and Targeting Resistance in Glioblastoma (UNITE Glioblastoma)
Subject Area
Medicine
Term
since 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 404521405
UNITE is driven by the strong vision that glioblastoma is treatable contrasting the fatalistic approach generally taken. Three key achievements from the first funding period stood out. UNITE researchers decisively shaped the concept of “cancer neuroscience” by defining key principles of cellular communications between glioblastoma cells but also between glioblastoma and host cells through tumor microtubes and bona fide synapses forming a network that fundamentally shapes biology and response to therapy. The discovery of this entirely new biological principle has already sparked a first clinical trial in patients with glioblastoma employing compounds disrupting such networks and breaking treatment resistance. UNITE researchers have developed a vaccine targeting mutated isocitrate dehydrogenase in gliomas successfully tested in a first-in-human phase 1 clinical trial following preclinical work demonstrating that this disease-defining mutation is a clonal neoepitope capable of generating mutation-specific T cell responses. UNITE researchers have developed and validated machine-learning tools to identify MRI imaging biomarkers of treatment response and outcome in large patient cohorts. Such tools are being transferred in daily clinical practice and decisively shape decision making in neurooncology. With the work of the first funding period in science and for talent development in the UNITE School of Neurooncology, which exceeded the premise of at least 50% female fellows, a further increase in the number of female PIs and PIs with a UNITE-related career development and further strategic appointments at MFHD/MFMA related to UNITE the Heidelberg campus and the selected partners have become even more suitable to tackle these challenges. The UNITE work packages of the second funding period will focus on unraveling mechanisms of intrinsic resistance with a stronger emphasis on the implications of hierarchically organized glioblastoma networks, neuronal-glioblastoma cell interaction and reverse translation from clinical trial information gathered in the first funding period; mechanisms of resistance conferred by the microenvironment integrating molecularly diverse glioblastoma entities and external treatment factors that shape the glioblastoma milieu; and develop, apply, and share state-of the art technological innovation with a focus on the integration of clinical and preclinical MR imaging, novel high-throughput technologies benefitting from the recent developments in functional phosphoproteomics, preclinical models, and analytical tools.
DFG Programme
Collaborative Research Centres
Current projects
- A01 - Targeting tumor cell network communication to overcome primary and adaptive resistance in glioblastoma (Project Heads Jung, Erik ; Osswald, Matthias ; Weil, Sophie ; Winkler, Frank )
- A02 - Development of a specific combination therapy for histone H3-mutant pediatric glioblastoma (Project Heads Jones, David ; Witt, Olaf )
- A03 - Deciphering resistance against targeted treatments (Project Heads Kessler, Tobias ; Wick, Wolfgang )
- A04 - Elucidating tumor-associated microglia interactions in astrocytomas CNS WHO-Grad 4 (Project Head Turcan, Ph.D., Sevin )
- A06 - Resistance Mechanisms of glioblastoma against alkylating agents and radiotherapy (Project Heads Goidts, Ph.D., Violaine ; Sahm, Felix )
- A07 - Mapping and targeting neuron-tumor networks to tackle therapy resistance in clioblastoma (Project Heads Karreman, Matthia ; Venkataramani, Varun )
- A08 - Personalized Glioblastoma treatment fuided by patient-derived tumor organoids (Project Heads Ernst, Aurélie ; Liu, Ph.D., Hai-Kun )
- B01 - Mechanisms of response and resistance to glioma-specific T-Cells (Project Heads Bunse, Theresa ; Platten, Michael )
- B03 - Targeting immunosuppressive programs in isocitrate dehydrogenase mutant gliomas (Project Heads Bunse, Lukas ; Pusch, Stefan )
- B04 - Impact of myeloid cells on the adaptive immune response in newly diagnosed and recurrent glioblastomas (Project Heads Herold-Mende, Christel ; Warta, Rolf )
- B06 - Visualization and Characterization of immune responses in H3K27M mutant gliomas (Project Heads Breckwoldt, Ph.D., Michael ; Sahm, Katharina )
- C01 - Comprehensive preclinical pharmacology testing of drugs used for glioblastoma treatment (Project Heads Bajraktari, Gzona ; Haefeli, Walter Emil ; Pfister, Stefan ; Sauter, Max )
- C02 - Radiomics, radiogenomics and deep-learning in neurooncology (Project Heads Bendszus, Martin ; Vollmuth, Philipp )
- C04 - Metabolic signaling in glioblastoma: a spatial multi-omics approach (Project Heads Hopf, Carsten ; Opitz, Christiane Agnes )
- C05 - Overcoming glioblastoma radio-resistance with particle therapy (Project Heads Abdollahi, Ph.D., Amir ; Dokic, Ph.D., Ivana )
- C06 - Functional Characterization of EGFR structural variants associated with long-term survival in glioblastoma, IDH-wt (Project Heads von Deimling, Andreas ; Reuß, David E. )
- D01 - Integrated tissue core (Project Heads von Deimling, Andreas ; Herold-Mende, Christel ; Hänggi, Daniel ; Ratliff, Miriam ; Sahm, Felix )
- D02 - Data Integration, bioinformatics analysis, and data exploration for precision neurooncology (Project Heads Buchhalter, Ivo ; Schlesner, Matthias )
- D03 - Integrated Research Training Group – UNITE School of Neurooncology (Project Heads Opitz, Christiane Agnes ; Wick, Wolfgang ; Zenz, Ph.D., Maja )
- D04 - Central administration project (Project Head Wick, Wolfgang )
Completed projects
- A05 - Predictive biomarkers for MGMT-promoter-methylated glioblastoma (Project Heads von Deimling, Andreas ; Reuß, David E. )
- B02 - DNA mis-match repair regulates immune checkpoint blockade therapy in glioblastoma (Project Head Liu, Ph.D., Hai-Kun )
- B05 - Dissecting the response of glioblastoma and its tumor microenvironment to focused high-dose radiotherapy (Project Heads Giordano, Frank ; Veldwijk, Marlon )
- C03 - Imaging immune signatures of glioma response and resistance towards immunotherapy (Project Head Breckwoldt, Ph.D., Michael )
Applicant Institution
Ruprecht-Karls-Universität Heidelberg
Participating University
Hochschule Mannheim; Universität Augsburg
Participating Institution
Deutsches Krebsforschungszentrum (DKFZ)
Spokesperson
Professor Dr. Wolfgang Wick