Research > Focus A > Work Packages A03
Summary
Patient tumor tissues from N²M², a trial using molecular defined treatments first-line with radiotherapy alone, are analyzed with single nuclei (sn) RNA sequencing next to comprehensive molecular analysis to understand resistance pathways and subclonal evolution under targeted therapies. Putative resistance pathways will be studied in vitro and in vivo. With a specific focus in understanding the role of senescent tumor cells promoting this targeted therapy resistance. In addition, molecular, metabolic and imaging biomarkers from two retrospective as well as one prospective study will be analyzed.
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
- 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
- cfDNA sequencing from cerebrospinal fluid
- Selective CRISPR/Cas9 knockouts
- 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
- Improvement of the treatment algorithm
- Bioinformatic implementation into a useful clinical application
PREVIOUS FUNDING PERIOD
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