Summary

The overarching goal of our research is to understand the biology of brain tumors and to rapidly translate these insights into clinical application. Current projects focus on intrinsic glioma treatment resistance and contribution of the glioma microenvironment to resistance. We investigate the molecular mechanisms of targeted therapies in glioblastoma, such as APG101, a soluble form of CD95, and on defining resistance signaling pathways, and mTOR/NDRG1/MGMT signaling for alkylating therapy (Weiler, Blaes PNAS 2014, Wick Clin Cancer Res 2014). The team around Frank Winkler (DFG funded Experimental Neurooncology Group) applies intravital microscopy with the main aim of unraveling growth and resistance patterns of glioma as well as critical steps in the formation of brain metastases and brain metastasis-brain-microenvironmental interactions (Osswald Nature 2015). Research done in collaboration with the Neuroradiology, Neuropathology, Proteomics and Epigenetics groups at DKFZ focuses on the development of diagnostic, prognostic and predictive biomarkers in anaplastic glioma and glioblastoma (Wick Neurology 2013; Capper Acta Neuropathol 2013; Wiestler Acta Neuropathol 2013; Wiestler Acta Neuropathol 2014). Studies on immunotherapies for brain tumors investigate checkpoint inhibition and personalized active immunotherapy based on next generation sequencing and target evaluation on the X-PRESIDENT platform (immatics, Tübingen) as well as IDHR132H directed peptide-based immunotherapy for patients with newly diagnosed malignant gliomas (Schumacher Nature 2014, Bunse J Clin Invest 2015). Research of the Max-Eder Junior Research Group Neurooncology of low grade Gliomas (Sevin Turcan) focuses on the role of IDH1 mutations in gliomagenesis (Bai Nat Genet 2016; Turcan Oncotarget 2013; Rohle Science 2013; Lu Nature 2012; Turcan Nature 2012). A particular strength of the Neurooncology program is the conduct of innovative clinical trials providing our patients access to novel treatment concepts. The focus lies on investigator-initiated concepts in collaboration with local (NCT/DKTK), national (Neurooncology Working Group of the German cancer Society) and international study groups (European Organization for Research and Treatment of Cancer). Exemplary, we have developed the NCT Neuro Master Match (N2M2) trial funded by Deutsche Krebshilfe, NCT 3.0 and DKFZ HIPO. N2M2 is an open label phase I/II umbrella trial for patients with newly diagnosed glioblastoma without MGMT promoter methylation. It aims at demonstrating safety, feasibility and preliminary efficacy of treatment with targeted compounds in addition to radiotherapy based on thorough molecular characterization. Future work will focus on characterization, development and exploration of novel biomarkers for guiding therapeutic decision-making and their potential use in primary and metastatic brain tumors.