Glioblastoma (GBM) is the most frequent, aggressive and lethal brain tumor. It has a universally fatal prognosis with 85% of patients dying within two years. Effective precision medicine therapies are thus urgently required.
The overall research objective of GLIORESOLVE project is to leverage a novel GBM tumor microenvironment (TME) classification system (developed during the recently completed Gliotrain Project), to establish new therapeutic strategies for GBM.
Key outcomes expected from GLIORESOLVE project are:
(1) to extend immunotherapy options to GBM patients and identify novel TME-subtype-specific therapeutic targets;
(2) develop and optimize state of the art pre-clinical models that recapitulate GBM TME-subtypes;
(3) test novel rationally selected (available) drugs / drug combinations for precision treatment of GBM based on TME-subtype assignment.
The consortium brings together leading European academics, clinicians, private sector and not-for-profit partners, and incorporates disruptive research methods including multi-omics, ex-vivo ‘tumor-on-a-chip’ assay development, computational modeling and systems biology.
GLIORESOLVE will provide a comprehensive translational research strategy that will go significantly beyond the current state-of-the-art in neuro-oncology, to establish a new TME-targeting precision medicine platform for this incurable disease.
The geneXplain’s sub-project within this great initiative it titled as “Modelling therapeutic resistance in GBM TME subtypes using multi-omics computational models”
We will be modelling the mechanisms of signaling and feedback loops between various cell types of the GBM TME and tumor cells in order to elucidate the key components of the interaction network to predict novel therapeutic targets and biomarkers across the TME subtypes.
Analysis will be conducted using the geneXplain platform that integrates statistical, bioinformatics, and systems biological modules with manually curated knowledge base on transcription factors and their binding sites (TRANSFAC® – gold standard in the field), and an in-depth database on intracellular signal transduction networks (TRANSPATH®).
Within the GLIORESOLVE project a new level of modeling will be introduced in the geneXplain platform supporting the modelling of cytokine/chemokine interactions between tumor and TME in the TME subtypes. TME-subtype specific interaction networks will be constructed and TME-subtype specific master regulators and drug targets will be identified by geneXplain GmbH within the project.