The NCT Brain Tumor Program holds a leading international position in terms of patient numbers, basic and translational research, trial activity, and innovation. The combination of new chairs and young investigators in neuropathology, molecular and clinical neurooncology, as well as research units in parvovirus research, molecular genetics, neuroimaging, and radiation oncology, have enabled DKFZ and its local partners to assemble a critical mass, install neurooncology as a prototypical interdisciplinary interaction with HUMS and NCT, and foster practice changes by precision medicine in immunotherapy, radiation oncology, and targeted therapies. The overall aim is to provide optimal diagnostics and treatment for all pediatric and adult patients with brain tumors through scientific excellence and high clinical and trial standards.
Clinical Cancer Research Program Brain Tumors
In addition to the outstanding data generated in the German ICGC project on pediatric brain tumors and the HIPO projects, the NCT Brain Tumor Program ensures a comprehensive research, diagnostics, translational, and clinical portfolio. This profile area has been further developed by an HUMS Experimental Neurooncology Professorship (F. Winkler) focusing on in vivo-2-photon microscopy, the transition of a Junior Group into another Clinical Cooperation Unit (Neuroimmunology and Brain Tumor Immunology, M. Platten), a DKFZ Professorship for Neurobiology of Brain Tumors (A. Martin-Villalba), a Junior Group for Brain Tumor Metabolism (C. Opitz), and strategic development of research groups that encompass neurooncology and radiology, radiation oncology, and neuropathology.
The groups headed by M. Platten, C. Opitz, and W. Wick have unraveled the relevance of the tryptophan metabolite kynurenin as an immunosuppressive and cancer-promoting agent and the first known endogenous ligand of the arylhydrocarbon receptor (Opitz, Litzenburger Nature 2011). The groups of A. von Deimling and W. Wick have spearheaded the translation of new molecular parameters in brain tumors into biomarkers, including the development of diagnostic tests (Capper Acta Neuropathol 2013; Wiestler Acta Neuropathol 2013; Wick Neurology 2013; Sahm Blood 2012), partially within HIPO projects. Originating from pediatric neurooncology, the program provides every newly diagnosed brain tumor patient with a genome-wide methylation analysis using 450 k arrays. Similarly, M. Bendszus and A. Radbruch have fostered the integration of novel MRI techniques into diagnosis and follow-up of brain tumor patients. A recent project established multi-parametric response maps, including advanced perfusion and spectroscopic techniques for molecularly-based imaging. These groups have joined forces to develop the preclinical basis and a first-in-man clinical trial with a peptide-based vaccine that targets mutant IDH in low-grade and anaplastic gliomas. A pilot will be translated into an immunotherapy trial at the DKTK sites. Coordinated from Heidelberg, the trial takes advantage of the peptide development within the Glioma Active Peptide Vaccination EU Consortium (GAPVAC) for personalized immunotherapy. All initiatives seek clinical progress, e.g. the Wick and Platten groups’ development of the first predictive biomarker for elderly glioblastoma patients (Wick Lancet Oncol 2012) and the APG101 trial of the Wick, Platten, Debus, von Deimling, Martin-Villalba, and Bendzsus groups with the soluble CD95 receptor together with radiotherapy – the first successful controlled trial in recurrent glioblastoma in 10 years – which also provides the basis for the development of a predictive biomarker (Wick ECCO 2013; Figure 2).
- Develop an oligogene signature (von Deimling JCO 2009) with novel epigenetic markers, methylated DNA binding-domain proteins (MBDs) and sequence-specific mass spectrometry (MassARRAY).
- Generate a database building on genomic and proteomic information from the Gene Glioma Network of the German Translational Cancer Research Consortium.
- Implement an oncolytic parvovirus H1 trial in glioblastoma patients; generate novel oncolytic viruses in cooperation with the Department of Translational Oncology and PEI.
- Design molecularly stratified trials (e.g., TGF-?/Notch/mTOR targets) with targeted substances, translating novel research findings into clinical practice.
- Provide evidence for the feasibility and efficacy of personalized immunotherapy.
- Improve and redefine treatment strategies for elderly patients.
- Develop joint efforts for pediatric and young adult patients with shared molecular profiles.