A unique collection of patient-derived brain tumour models to accelerate drug development

Summary: The NORLUX Neuro-Oncology Laboratory at the Luxembourg Institute of Health (LIH) Department of Oncology, in collaboration with multiple local and international partners, established a large collection of patient-derived glioma organoids and xenograft models that mimic the specific features of patient brain tumours. The findings were published in October 2020 in the international journal Acta Neuropathologica, with the full title “Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology”. Models are available on a collaborative basis and can be browsed on the new EurOPDX Data Portal. 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.

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 currently established a comprehensive cohort of over 40 of 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 tumours. The cohort includes PDOXs from primary and recurrent gliomas, at different stages, from different subtypes and carrying different genetic mutations. 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.

“Brain cancer organoids and the resulting mouse avatars have a unique value as a drug screening platform in both preclinical and co-clinical studies. This is illustrated by some examples in our recent research article”, states Dr Anna Golebiewska, Group Leader at NORLUX and co-first author of the scientific publication.

“Our work is the result of a distinctive interdisciplinary approach based on the complementary competences of Luxembourg’s biomedical research ecosystem”, explain Dr Ann-Christin Hau and Mrs Anaïs Oudin of the NORLUX research team and co-first authors of the publication. “(…) Most importantly, we would like to extend our gratitude to all the patients and their families for making our study possible with their participation”, they add.

The NORLUX team at LIH have been members of the EurOPDX Consortium for several years. One of the main objectives of EurOPDX is to increase and facilitate collaborative research using PDX models, notably by developing a public repository to showcase the established models and their associated metadata and molecular data. The collection of 40 PDOX glioma models and associated data is indeed available to the international scientific community on the new EurOPDX Data Portal. Researchers at NORLUX can be contacted directly from the Portal to discuss potential collaborations to advance research on and treatment of brain tumours. Models are also available on the PDXFinder.

“By sharing our models and data and joining forces with leading international partners in initiatives like the Horizon 2020-funded EurOPDX consortium and the Glioma Longitudinal AnalySiS (GLASS) consortium, we are continuously contributing to increasing the availability and use of these invaluable resources at the global level, thereby tangibly supporting breakthroughs in personalised cancer therapy”, concludes Prof Simone Niclou, Director of the LIH Department of Oncology (DONC) and corresponding author of the publication.

Image legend: 3D organoids during drug treatment (viable cells = green, dead cells = red); Group picture, from left to right: Dr Anna Golebiewska, Anaïs Oudin, Dr Ann-Christin Hau and Prof Simone Niclou.