GLIOTRAIN consortium member, the Luxembourg Institute of Health (LIH), establishes a collection of preclinical patient-derived brain tumour models to accelerate drug development

Dr Anna Golebiewska and Prof Simone Niclou and GLIOTRAIN ESR Yahaya Yabo from the NORLUX Neuro-Oncology Laboratory at the LIH Department of Oncology (DONC), along with key collaborators, have established a large collection of patient-derived glioma organoids and xenograft models that mimic the specific features of patient brain tumours. The work was undertaken in collaboration with the Centre Hospitalier de Luxembourg (CHL), the Laboratoire National de Santé (LNS), the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg and other international partners. These tools will allow the establishment of personalised drug efficacy studies, thus increasing the chances of success of clinical trials and improving clinical outcomes for patients. The findings were presented in a recent publication “Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology”, in the international peer-reviewed journal Acta Neuropathologica. You can read the full press release from the Luxembourg Institute of Health here

From left to right: Dr Anna Golebiewska, Anaïs Oudin, Dr Ann-Christin Hau (joint first authors) and Prof Simone Niclou (senior author)
GLIOTRAIN PhD candidate, Yahaya Yabo (co-author)

Advancing personalised cancer treatment through patient “avatars”.

Clinical trials are crucial in order to test the efficacy of novel therapeutic molecules directly on patients. Nevertheless, their success is significantly dependent on the quality of the results obtained during preclinical drug testing studies carried out on experimental models of a patient’s tumour prior to the clinical phase. The availability of accurate and comprehensive models in the preclinical setting that reflect the full range of genetic variations observed in brain cancers and that are able to reliably predict the sensitivity of specific types of tumours to new personalised treatments is therefore of utmost importance in the context of translational oncology. 

To address this currently unmet need, NORLUX has been working in close cooperation with the Centre Hospitalier de Luxembourg (CHL) and the major research institutes in Luxembourg to establish a collection of brain tumours from over 1000 patients. Through the samples provided by the Neurosurgery department of the CHL, NORLUX has been generating a biobank of brain tumour organoids – three-dimensional tissue cultures derived from viable cells from patient tumours.  Tumour organoids are subsequently implanted in immunodeficient mice to give rise to so-called Patient-Derived Orthotopic Xenografts (PDOXs). NORLUX have established a comprehensive cohort of over 40 PDOXs from malignant gliomas including glioblastoma, one of the deadliest forms of brain cancer. These models act as clinically relevant patient ‘avatars’, faithfully reproducing the main biological, histological and genomic features of the original patient tumors. Unique PDOXs derived from tumour samples of the same patient prior to and after treatment are also available, improving the understanding of how specific cancers respond to various treatments, according to their genetic characteristics.

A microscopic view of the organoids: treatment over time L - R (Living cells = green, dead cells = red)

The collection of 40 PDOX glioma models and associated data is available to the international scientific community on PDXfinder, an open global catalogue co-developed by the European Molecular Biology Laboratory - European Bioinformatics Institute (EMBL - EBI) and the Jackson Laboratory.

This study was supported by grants from the Télévie-FNRS, the Fondation Cancer Luxembourg, the Luxembourg National Research Fund and the EU H2020-funded GLIOTRAIN ITN.