Research > Focus C > Work Packages C05
Summary
This project aims to explore the potential of particle radiotherapy, i.e., the parameter space, radiation quality, dose, dose-rate and linear energy transfer (LET, ionization density along the track) to overcome glioblastoma treatment resistance by eradicating the radioresistant tumor subpopulations and forming an immune permissive niche via reprograming of the tumor immune microenvironment while optimally sparing normal tissue.
Task 1
Radiobiological optimization of GB therapeutic window with personalized particle RT
Steps / Workflow
Biophysical characterization of radiation response:
- Dose, LET, Dose-rate
- DNA Damage Repair (DDR) Kinetics
- Deciphering the MoA via integrative Omics
- Impelement 3D personalized GB Models
- Develop predictive models for GB response to particle RT parameter space (UNIVERSE)
Task 2
Remodeling GB tumor microtube network with particle RT
Steps / Workflow
- Characterize particle RT effect on formation of complex nonrepairable DNA – damage clusters and their relevance for microtube formation in vivo
- Analyze differential pathways triggered by DDR and their impact on cell survival signals throughout the microtube network
Task 3
Mechanisms of GB resistance at the tumor-stroma interface
Steps / Workflow
- Evaluate the impact of high- LET RT to eradicate radioresistant GB subpopulations forming an immuno-permissive niche
- Spatial deconvolution of TIME response to particle RT at single cell resolution
- Reprogram TIME to synergize with immunogenic effects of high-LET particle RT towards development of novel in-situ tumor vaccination strategies
Task 4
Development of biomarker of GB response to RT
Steps / Workflow
- Integrative omics analysis of tumor evolution under RT
- Optimizing tumor delineation for high precision particle RT
- Longitudinal spatio-temporal tracking of tumor and normal tissue evolution with respect to particle RT dose distribution and quality (biophysical model)
Previous funding period
PRINCIPLE INVESTIGATORS
BAJRAKTARI-SYLEJMANI, GZONA, DR. RER. NAT.
Group Leader
Heidelberg University Hospital, Department of Clinical Pharmacology and Pharmacoepidemiology, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
DOKIC, IVANA, DR. RER. NAT.
Postdoctoral reseacher
Heidelberg University Hospital, Division of Molecular and Translational Radiation Oncology Heidelberg Ion-Beam Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany