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Annual Report 2019

Project UNITE – together against glioblastomas

Banner Project UNITE, 3 young physicians doing research in front of a computer (photo)
Banner Project UNITE, 3 young physicians doing research in front of a computer
Banner Project UNITE, 3 young physicians doing research in front of a computer

Impulses for the treatment of brain tumors

Project UNITE – together against glioblastomas

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Tumor cells called glioblastomas have surprising capabilities, which even remind some experts of a kind of “second brain”. In Project UNITE, researchers at the new collaborative research center 1389 under the leadership of Heidelberg University Hospital concentrate their knowledge and their creative ideas in order to find effective new therapies against these cancer cells.

We spoke with Prof. Dr. Wolfgang Wick, the speaker of this new collaborative research center. Project partners are the Deutsche Krebsforschungszentrum (German Cancer Research Center / DKFZ), Mannheim University and the Medical Faculty of Mannheim at Heidelberg University.

Portrait Prof. Dr. Wolfgang Wick

Prof. Dr. Wolfgang Wick is Managing Director of the Department of Neurology and Head of the Cllinical Cooperation Unit for Neuro-Oncology at the German Cancer Research Center (DKFZ).

Herr Prof. Wick, what does UNITE stand for?

UNITE means to band together or to join forces and this is precisely what we want to achieve with this new collaborative research center. In the coming four years, we want to bring together the expertise of scientists from Heidelberg and Mannheim in order to better understand glioblastomas and to develop treatment strategies. This unique alliance of experts in the field of Neuro-oncology is also reflected in our organization: Co-Speakers of UNITE are Prof. Dr. Michael Platten, Director of the Department of Neurology at Mannheim University Hospital and Head of a Clinical Cooperation Unit at the DKFZ and Prof. Dr. Stefan Pfister, Director of the Hopp Children’s Cancer Center at Heidelberg. The German Research Foundation is providing about eleven million euros for our project.

Why are glioblastomas so difficult to treat?

The following applies to all brain tumors: The cancer grows where we locate the center of our personality, and a disease in the “central steering organ” triggers great fears in everybody. In contrast to other, frequently even benign brain tumors, glioblastoma in children and adults is a severe and mostly fatal disease, however. There are no known risk factors and both children and older persons are affected, who are then suddenly removed from their everyday life. In addition, there is the special structure of these tumors …

Some experts refer to glioblastomas as a “second brain”, am I right?

Indeed, there are similarities which never fail to fascinate us neuroscientists. We were able to determine, for example, that the tumor cells frequently appear with a widely branched structure, are linked to each other through a kind of tubular system, and can even move in the brain. In a current publication researchers at the Hospital and the Medical Faculty of Heidelberg even demonstrated that the brain’s nerve cells enter into contact with the tumor cells. In this way, the nerve cells send signals to the cancer cells and the tumor benefits from this “input”: the activation signals are probably a driving force for tumor growth and the invasion of healthy brain tissue by tumor cells.

News of the publication (German): “Nervenzellen feuern Hirntumorzellen zum Wachstum an”

Heidelberg and Mannheim: Center for brain-tumor research in the Kurpfalz Region

At the Heidelberg/Mannheim site, there is a unique network of research groups that focus on research and care for persons suffering from brain cancer. There are numerous project-related collaborations across the boundaries of these groups and many medical and natural science theses for a bachelor’s, a master’s, and a doctoral degree are supervised jointly. As part of the new Collaborative Research Center, the “UNITE Post-Graduate Program in Neuro-Oncology” will support outstanding talents, the scientific dialogue, and interdisciplinary training.

In doing so, the University Hospital will be supported by the Hertie-Stiftung and the Else-Kröner-Fresenius-Stiftung



What does the new collaborative research center want to do differently?

Our research project assumes that there are sub-classes of patients with a clear treatment benefit – at least for a certain period of time – both through radiation and chemotherapy and also through experimental, targeted, or immunotherapy treatment strategies. Our goal: We want to break down the disease into individual diseases, because the real cases in the hospitals show that the patients respond very differently to treatments. We have to get to know our opponent better! A second aspect is that we want to find new medications because many of the currently used substances actually come from the Stone Age, when seen from the pharmacological perspective.

Doctors in front of brain tumorscan (photo)

Goal of the new Collaborative Research Center:
Breaking down the glioblastoma phenomenon into individual diseases.

How do you do this?

We will focus less on research into the causes, because unfortunately there still are no possibilities for prevention and no early detection options for glioblastomas. What we are interested in is obtaining an improvement in the prospects for patients who are already ill: How can we grasp the various sub-types of glioblastomas using molecular-biological markers? Where do the respective weak spots lie and how can we attack there? In all, there will be 20 sub-projects based on three equal cornerstones: We use a uniform, common tissue platform comprising 100 samples, process our hypothesis on the highest technical level, and concentrate on implementable results.

Representation of the UNITE cooperations (graphic)

An overview of the UNITE collaboration

The UNITE projects form a focus for the understanding of the resistance mechanisms of glioblastomas (Focus A) and the decoding of the resistance mechanisms in the tumor environment (Focus B). In Focus C, novel high-throughput technology, preclinical models, and analysis procedures are developed and applied based on currently available technical processes. In Core Area D, central projects provide quality-assured tissue and data for the development of precision medicine.

  • Focus A

  • Focus B

  • Focus C

  • Core AreaD

Resistance mechanisms of glioblastomas to treatment


Targeting tumor cell networks to overcome primary and adaptive resistance in glioblastoma

Dr. med. Erik Jung, Prof. Dr. med. Frank Winkler, University Hospital Heidelberg


Development of a specific combination therapy for histone H3-mutant Pediatric glioblastoma

David T. W. Jones, PhD, Prof. Dr. med. Olaf Witt,
Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)


Deciphering resistance against targeted treatments

Dr. med. Tobias Kessler, Prof. Dr. med. Wolfgang Wick, University Hospital Heidelberg


Evolution of IDH mutant gliomas during malignant progression

Sevin Turcan, PhD, University Hospital Heidelberg


Predictive biomarkers for MGMT promoter-methylated glioblastoma

Prof. Dr. med. Andreas Von Deimling, PD Dr. med. David E. Reuss, University Hospital Heidelberg


Resistance mechanisms of glioblastoma against alkylating agents and radiotherapy

Dr. biol. hum. Violaine Goidts, German Cancer Research Center (DKFZ), PD Dr. med. Felix Sahm, University Hospital Heidelberg

Decoding resistance mechanisms in the tumor environment


Mechanisms of response and resistance to checkpoint blockade in gliomas

Dr. rer. nat. Theresa Bunse, Prof. Dr. Michael Platten, Mannheim University Hospital


DNA mis-match repair regulates immune checkpoint blockade therapy in glioblastoma

Hai-Kun Liu, PhD, German Cancer Research Center (DKFZ)


Targeting immunsuppressive programs in isocitrate dehydrogenase mutant gliomas

Dr. rer. nat. Stefan Pusch, Dr. med. Lukas Bunse,
University Hospital Heidelberg


Impact of myeloid cells on the adaptive immune response in IDH1-mutant glioblastomas

Prof. Dr. rer. nat. Christel Herold-Mende, Dr. sc. hum. Rolf Warta, Heidelberg University Hospital


Dissecting the response of glioblastoma and its tumor microenvironment to focused high-dose radiotherapy

Prof. Marlon R. Veldwijk, Mannheim University Hospital

Novel high-throughput technology, preclinical models and analysis procedures


Comprehensive preclinical pharmacology testing of drugs used for glioblastoma treatment in children and adults

Prof. Dr. med. Stefan M. Pfister, Hopp-Children´s Comprehensive Cancer Center at the NCT Heidelberg,
Prof. Dr. med. Walter E. Haefeli, University Hospital of Heidelberg


Radiomics, radiogenomics and deep-learning in Neuro-oncology

Prof. Dr. med. Martin Bendszus, Dr. med. Philipp Kickingereder, University Hospital Heidelberg


Imaging immune signatures of glioma response and resistance towards immunotherapy

Dr. med. Michael Breckwoldt, PhD, University Hospital Heidelberg


Identification and spatial mapping of metabolic resistance factors by MALDI mass spectrometry imaging

Prof. Dr. rer. nat. Carsten Hopf, Hochschule Mannheim,
Dr. med. Christiane A. Opitz, German Cancer Research Center (DKFZ)


Overcoming glioma radio-resistance with particle therapy

Dr. med. Dr. rer. nat. Amir Abdollahi, Dr. rer. nat. Ivana Dokic, University Hospital Heidelberg, Radiationoncology, UKHD

Central projects to provide quality-assured tissue and data on the development of precision medicine


Integrated tissue and patient derived model core

Prof. Dr. med. Andreas Von Deimling, University Hospital Heidelberg, Dr. med. Miriam Ratliff, Mannheim University Hospital, Prof. Dr. rer. nat. Christel Herold-Mende, University Hospital Heidelberg


Data integration, bioinformatics analysis, and data exploration for precision neurooncology

Dr. rer. nat. Matthias Schlesner, German Cancer Research Center (DKFZ)


Integrated research training group – unite school of neurooncology

Prof. Dr. med. Wolfgang Wick, Maja Zenz, PhD, University Hospital Heidelberg



Prof. Dr. Wolfgang Wick, Dr. Maja Zenz, University Hospital Heidelberg

Team 03 Medical Physicist and MTRA

Impulses from strong teams

Swantje Ecker

Medical Physicist

Sabine Kuhn

Medico-Technical Radiology Assistant (MTRA)

Among other places, glioblastomas are being treated in the Heidelberg Ion Beam Therapy Center (HIT). So that the ion beam can develop its power precisely in the tumor, Swantje Ecker and Sabine Kuhn work closely together. Together they find the perfect position for the patients and optimize the fields of radiation. In addition to all of the technology, they take away the fears of children regarding the treatment with their warm hearts.