Research > Focus A > Work Packages A03
Summary
In this project, preclinical models and NCT Neuro MASTER Match (N2M2) study cohort-derived tissues of patients with newly diagnosed and recurrent glioblastoma will be used to decipher molecular, cellular and imaging determinants of response and resistance to precision treatments in glioblastoma. With this research, patient groups likely to benefit from a molecularly targeted intervention will be characterized, predictive biomarkers selected and prioritized, and parallel as well as subsequent treatments will be developed to enhance therapeutic benefit in selected molecularly defined subgroups. The visual abstract below shows the aims and planned tasks of the work package.
Task 1
Discovering and understanding mechanisms underlying response and resistance in selected study cohorts and PDX models
Steps / Workflow
- Molecular, proteomic, metabolomic and single cell analysis of patient samples and PDX
- Characterization of heterogeneity
- CRISPR/Cas9 drug screening
- Integrated data analysis for description of N2M2 treatment resistance
Task 2
Analysis of primary and recurrent N2M2 samples on molecular and radiomic level to study tumor evolution and resistance
Steps / Workflow
- Molecular, proteomic, metabolomic and imaging data of recurrent tumors after N2M2 treatment
- Identification of patterns of response and resistance against targeted treatments
Task 3
Development of sequential treatment algorithms and discovery of new targets
Steps / Workflow
- New compounds screening with focus on epigenetic modifiers
- CRISPR/Cas9 screening to identify resistance markers against new agents
- Testing of possible sequential treatments
Task 4
Developing a sensitivity/resistance molecular and imaging signature and implementation into a multiparametric algorithm for best treatment allocation
Steps / Workflow
- Literature review and data integration of tasks 1-3
- Development of a treatment algorithm
- Bioinformatic implementation into a clinical useful application
PRINCIPLE INVESTIGATORS
KESSLER, TOBIAS, DR. MED.
Post Doc / Resident
University Hospital Heidelberg, Department of Neurology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
Wick, Wolfgang, Prof. Dr. med.
UNITE Spokesperson & Chairman
University Hospital Heidelberg, Department of Neurology / Neurooncology & DKFZ, Clinical Cooperation Unit Neurooncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany