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Themen
Research
- Focus A
- A01: Targeting tumor cell network communication to overcome primary and adaptive resistance in glioblastoma
- A02: Development of a specific combination therapy for histone H3-mutant pediatric glioblastoma
- A03: Deciphering resistance against targeted treatments
- A04: Elucidating tumor-associated microglia interactions in astrocytomas CNS WHO-grade 4
- A05: Predictive biomarkers for MGMT-promoter-methylated glioblastoma (2019 – 2023)
- A06: Resistance mechanisms of glioblastoma against alkylating agents and radiotherapy
- A07: Mapping and targeting neuron-tumor networks to tackle therapy resistance in glioblastoma
- A08: Personalized glioblastoma treatment guided by patient-derived tumor organoids
Research
- Focus B
- B01: Mechanisms of response and resistance to glioma-specific t cells
- B02: DNA mis-match repair regulates immune checkpoint blockade therapy in glioblastoma (2019 – 2023)
- B03: Targeting immunosuppressive programs in isocitrate dehydrogenase mutant gliomas
- B04: Impact of myeloid cells on the adaptive immune response in newly diagnosed and recurrent glioblastomas
- B05: Dissecting the response of glioblastoma and its tumor microenvironment to focused high-dose radiotherapy (2019 – 2023)
- B06: Visualization and characterization of immune responses in H3K27M mutant gliomas
Research
- Focus C
- C01: Comprehensive preclinical pharmacology testing of drugs used for glioblastoma treatment
- C02: Radiomics, radiogenomics and deep-learning in neurooncology
- C03: Imaging immune signatures of glioma response and resistance towards immunotherapy (2019 – 2023)
- C04: Metabolic signaling in glioblastoma: a spatial multi-omics approach
- C05: Overcoming glioma radio-resistance with particle therapy
- C06: Functional characterization of EGFR structural variants associated with long-term survival in glioblastoma, IDH-WT
SUPERIORITY OF TEMOZOLOMIDE OVER RADIOTHERAPY FOR ELDERLY PATIENTS WITH RTK II METHYLATION CLASS, MGMT PROMOTER-METHYLATED MALIGNANT ASTROCYTOMA
ResearchResearch findings related to clinical trial development within UNITE
O6-methylguanine DNA-methyl transferase (MGMT) promoter methylation status is predictive for alkylating chemotherapy, but there are non-benefitting subgroups. The long-term update of NOA-08 compared efficacy and safety of radiotherapy (RT, n=176) and temozolomide at 7/14 days (TMZ, n=193) in patients >65 years with anaplastic astrocytoma or glioblastoma. DNA methylation patterns and copy number variations were assessed in the biomarker cohort of 104 patients and in an independent cohort of 188 patients treated with RT+TMZ-containing regimens in Heidelberg. Wick et al. showed that MGMT promoter methylation is a strong predictive biomarker for the choice between RT and TMZ. It indicates favorable long-term outcome with initial TMZ monotherapy in patients with MGMT promoter-methylated tumors primarily in the RTK II subgroup.
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GLUTAMATERGIC SYNAPTIC INPUT TO GLIOMA CELLS DRIVES BRAIN TUMOUR PROGRESSION
ResearchResearch findings related to UNITE work package A01
A network of communicating tumour cells that is connected by tumour microtubes mediates the progression of incurable gliomas. Moreover, neuronal activity can foster malignant behaviour of glioma cells by non-synaptic paracrine and autocrine mechanisms. Here Kuner et al. report a direct communication channel between neurons and glioma cells in different disease models and human tumours: functional bona fide chemical synapses between presynaptic neurons and postsynaptic glioma cells. These neurogliomal synapses show a typical synaptic ultrastructure, are located on tumour microtubes, and produce postsynaptic currents that are mediated by glutamate receptors of the AMPA subtype. Neuronal activity including epileptic conditions generates synchronised calcium transients in tumour-microtube-connected glioma networks. Glioma-cell-specific genetic perturbation of AMPA receptors reduces calcium-related invasiveness of tumour-microtube-positive tumour cells and glioma growth. Invasion and growth are also reduced by anaesthesia and the AMPA receptor antagonist perampanel, respectively. These findings reveal a biologically relevant direct synaptic communication between neurons and glioma cells with potential clinical implications.
LINK TO PUBLICATION