Glioma patient avatars for personalized medicine

The high failure of therapeutic agents in clinical trials is often linked to inappropriate model systems used in the preclinical setting. Hence experimental models better reflecting human tumor biology are an unmet need. Over the years, our lab has set up a living biobank of brain tumor organoids from over 600 patients and has generated a large cohort (>40) of Patient-Derived Orthotopic Xenografts (PDOXs) for malignant gliomas (Glioblastoma and IDH-mutant high-grade gliomas). PDOX models enable long-term propagation of patient tumors and represent clinically relevant patient avatars. The NORLUX PDOX cohort contains tumors with different genetic, epigenetic and transcriptomic background recapitulating molecular subtypes of glioma tumors in patients. Our cohort also comprises unique PDOXs derived from matched longitudinal samples of the same patient prior and after treatment. PDOXs allow to interrogate biological mechanisms of human tumor development in the brain microenvironment, functional validation studies and drug efficacy studies, including aspects of brain penetrance. Currently we are expanding our live biobank to obtain models representative of rarer glioma subtypes. We further plan to adapt the PDOX models to humanized immune-microenvironment, allowing for analysis and testing of novel immunotherapies.

This project is supported by the Luxembourg Institute of Health, Télévie FNRS (7.8513.18) and the Personalised Medicine Consortium Pump-Prime.

NORLUX glioma PDOX models are available at PDXFinder database.

NORLUX is a member of the EurOPDX consortium.  

 

Key publications

Golebiewska, Hau, Oudin et al., BioRvix, 2020 link
Bougnaud et al., Oncotarget, 2016 pubmed
Fack et al., EMBO Mol Med, 2015 pubmed
Demeure et al.,  MCP, 2015  pubmed
Navis et al., ANC, 2013 pubmed
Golebiewska et al., Brain, 2013 pubmed
Keunen et al., PNAS, 2011 pubmed
Niclou et al., FASEB J, 2008 pubmed