Preclinical services for advancing cancer treatment for patients with brain tumours.
The high failure of therapeutic agents during clinical trials is frequently linked to inappropriate model systems used in the preclinical phase. Consequently, there is a pressing need for experimental models that more accurately reflect human tumour biology. Our approach involves utilizing a comprehensive collection of patient tumours and blood samples, combined with the creation of clinically relevant models. This enables us to provide a precise evaluation of novel therapies and biomarkers at the preclinical stage. Our strategy is geared towards enhancing the effectiveness of future clinical trials.
Over the years, the NORLUX laboratory has collected tumour tissue and blood specimens from over 1200 central nervous tumours (PRECISION-PDX study) available for research. It has established a living biobank of primary tumour organoids from over 700 tumours, including primary brain tumours (i.e. gliomas, meningiomas, ependynomas, rare cancers) and brain metastases.
Focusing on malignant gliomas, the laboratory has generated a large cohort (>45) of well-characterized Patient-Derived Orthotopic Xenografts (PDOXs) including IDH-wild-type glioblastomas and IDH-mutant high-grade gliomas. PDOX models enable long-term propagation of patient tumours and represent clinically relevant patient avatars. The LIH-NORLUX PDOX cohort contains tumours with different genetic, epigenetic and transcriptomic background recapitulating molecular subtypes and histopathological features of glioma tumours in patients. Our cohort also comprises unique PDOXs derived from matched longitudinal samples of the same patient prior and after treatment. Currently we are expanding our live biobank to obtain established models representative of rarer glioma subtypes and other brain tumours.
Our unique protocols allow for versatile functional readouts and drug efficacy investigations in vivo (as xenografts) and ex vivo (as organoids and short-tem stem-like cultures), while preserving key characteristics of patient tumours. We are able to reconstitute humanized immune-microenvironment in vivo and ex vivo, allowing for analysis and testing of novel immunotherapies.
LIH-NORLUX models are available at the Patient-Derived Cancer Model (PDCM) Finder.
NORLUX is a member of the EurOPDX consortium.